bluuebunny/crossref_metadata_2025 huggingface dataset:
‘It’s about time’: policymakers’ and health practitioners’ perspectives on implementing fertility care in the Gambian health system
Authors: Afferri Anna , Dierickx Susan , Allen Haddijatou , Bittaye Mustapha , Marena Musa , Pacey Allan , Balen Julie
Published: March 2024

Background

Infertility is a major health issue worldwide, yet very few examples of interventions addressing infertility in the Global South have been documented to date. In The Gambia, West Africa, infertility is recognised as a burden and the health authorities have included it in several health policies and the new National Reproductive Health Strategy however, a detailed operationalisation plan for fertility care has not yet been established. Here, we aim to understand and document the factors that influence the implementation of fertility care in The Gambia.

Methods

We conducted 46 semi-structured interviews with policymakers, implementers, and health practitioners in both the public and private sectors from July to November 2021. The interviews were transcribed, anonymised and analysed with NVivo Pro version 1.6.1. The analysis was initially inductive, with themes arising from the coding categorised according to the WHO health systems building blocks framework.

Results

This study identified several barriers to a successful implementation of fertility care in The Gambia, including (i) a lack of routinely collected infertility data; (ii) an absence of financial protection mechanisms for patients, and/or a specific budget for infertility; (iii) limited cooperation between the public and private sectors in the provision of fertility care; and (iv) gaps in fertility care training among health practitioners. Conversely, enablers included: (i) strong national infertility leadership; and (ii) the integration of infertility care within public reproductive health services.

Conclusion

The Gambian health system is not yet in the position to support a comprehensive fertility care package in its public health facilities. Several aspects of the implementation of fertility care must be considered in operationalising the health strategy including the systematic collection of infertility data, fertility awareness, and the provision of specialised fertility care training. Furthermore, a stronger partnership between the public and private sectors must be developed. Given the increasing availability of assisted reproductive technologies in the sub-Saharan Africa region, and the tendency to locate these technologies in the private sector, further research is needed to understand and identify the processes underlying the implementation of fertility care and to foster better integration with the existing health system.
Origin and diversity of Capsella bursa-pastoris from the genomic point of view
Authors: Penin Aleksey A. , Kasianov Artem S. , Klepikova Anna V. , Omelchenko Denis O. , Makarenko Maksim S. , Logacheva Maria D.
Published: March 2024

Background

Capsella bursa-pastoris, a cosmopolitan weed of hybrid origin, is an emerging model object for the study of early consequences of polyploidy, being a fast growing annual and a close relative of Arabidopsis thaliana. The development of this model is hampered by the absence of a reference genome sequence.

Results

We present here a subgenome-resolved chromosome-scale assembly and a genetic map of the genome of Capsella bursa-pastoris. It shows that the subgenomes are mostly colinear, with no massive deletions, insertions, or rearrangements in any of them. A subgenome-aware annotation reveals the lack of genome dominance—both subgenomes carry similar number of genes. While most chromosomes can be unambiguously recognized as derived from either paternal or maternal parent, we also found homeologous exchange between two chromosomes. It led to an emergence of two hybrid chromosomes; this event is shared between distant populations of C. bursa-pastoris. The whole-genome analysis of 119 samples belonging to C. bursa-pastoris and its parental species C. grandiflora/rubella and C. orientalis reveals introgression from C. orientalis but not from C. grandiflora/rubella.

Conclusions

C. bursa-pastoris does not show genome dominance. In the earliest stages of evolution of this species, a homeologous exchange occurred; its presence in all present-day populations of C. bursa-pastoris indicates on a single origin of this species. The evidence coming from whole-genome analysis challenges the current view that C. grandiflora/rubella was a direct progenitor of C. bursa-pastoris; we hypothesize that it was an extinct (or undiscovered) species sister to C. grandiflora/rubella.
Autoimmune diseases and adverse pregnancy outcomes: an umbrella review
Authors: Singh Megha , Wambua Steven , Lee Siang Ing , Okoth Kelvin , Wang Zhaonan , Fayaz Fathima Fazla Ahamed , Eastwood Kelly-Ann , Nelson-Piercy Catherine , Reynolds John A. , Nirantharakumar Krishnarajah , Crowe Francesca ,   on behalf of MuM-PreDiCT
Published: March 2024

Background

There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely studied. However, few autoimmune conditions/adverse outcomes have been studied more than others, and this umbrella review aims to consolidate existing knowledge in this area with the aim to provide new knowledge and also identify gaps in this research area.

Methods

Medline, Embase, and Cochrane databases were searched from inception to December 2023. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR) with 95% confidence intervals were reported.

Results

Thirty-two reviews were included consisting of 709 primary studies. The review reported the association between 12 autoimmune conditions and 16 adverse pregnancy outcomes. Higher risk of miscarriage is reported in women with Sjögren’s syndrome RR 8.85 (95% CI 3.10–25.26) and systemic lupus erythematosus (SLE) OR 4.90 (3.10–7.69). Pre-eclampsia was reported higher in women with type 1 diabetes mellitus (T1DM) OR 4.19 (3.08–5.71) and SLE OR 3.20 (2.54–4.20). Women reported higher risk of diabetes during pregnancy with inflammatory bowel disease (IBD) OR 2.96 (1.47–5.98). There was an increased risk of intrauterine growth restriction in women with systemic sclerosis OR 3.20 (2.21–4.53) and coeliac disease OR 1.71 (1.36–2.14). Preterm birth was associated with T1DM OR 4.36 (3.72–5.12) and SLE OR 2.79 (2.07–3.77). Low birth weight babies were reported in women with women with SLE or systemic sclerosis OR 5.95 (4.54–7.80) and OR 3.80 (2.16–6.56), respectively. There was a higher risk of stillbirth in women with T1DM OR 3.97 (3.44–4.58), IBD OR 1.57 (1.03–2.38), and coeliac disease OR 1.57 (1.17–2.10). T1DM in women was associated with 32% lower odds of small for gestational age baby OR 0.68 (0.56–0.83).

Conclusions

Pregnant women with autoimmune conditions are at a greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to postnatal care for women with autoimmune conditions.
The role of lifestyle in the association between long-term ambient air pollution exposure and cardiovascular disease: a national cohort study in China
Authors: Hu Xiangming , Knibbs Luke D. , Zhou Yingling , Ou Yanqiu , Dong Guang-Hui , Dong Haojian
Published: March 2024

Background

Cardiovascular disease (CVD) caused by air pollution poses a considerable burden on public health. We aim to examine whether lifestyle factors mediate the associations of air pollutant exposure with the risk of CVD and the extent of the interaction between lifestyles and air pollutant exposure regarding CVD outcomes.

Methods

We included 7000 participants in 2011–2012 and followed up until 2018. The lifestyle evaluation consists of six factors as proxies, including blood pressure, blood glucose, blood lipids, body mass index, tobacco exposure, and physical activity, and the participants were categorized into three lifestyle groups according to the number of ideal factors (unfavorable, 0–1; intermediate, 2–4; and favorable, 5–6). Satellite-based spatiotemporal models were used to estimate exposure to ambient air pollutants (including particles with diameters ≤ 1.0 μm [PM1], ≤ 2.5 μm [PM2.5], ≤ 10 μm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cox regression models were used to examine the associations between air pollutant exposure, lifestyles and the risk of CVD. The mediation and modification effects of lifestyle categories on the association between air pollutant exposure and CVD were analyzed.

Results

After adjusting for covariates, per 10 μg/m3 increase in exposure to PM1 (HR: 1.09, 95% CI: 1.05–1.14), PM2.5 (HR: 1.04, 95% CI: 1.00–1.08), PM10 (HR: 1.05, 95% CI: 1.03–1.08), and NO2 (HR: 1.11, 95% CI: 1.05–1.18) was associated with an increased risk of CVD. Adherence to a healthy lifestyle was associated with a reduced risk of CVD compared to an unfavorable lifestyle (HR: 0.65, 95% CI: 0.56–0.76 for intermediate lifestyle and HR: 0.41, 95% CI: 0.32–0.53 for favorable lifestyle). Lifestyle played a significant partial mediating role in the contribution of air pollutant exposure to CVD, with the mediation proportion ranging from 7.4% for PM10 to 14.3% for PM2.5. Compared to an unfavorable lifestyle, the relative excess risk due to interaction for a healthier lifestyle to reduce the effect on CVD risk was − 0.98 (− 1.52 to − 0.44) for PM1, − 0.60 (− 1.05 to − 0.14) for PM2.5, − 1.84 (− 2.59 to − 1.09) for PM10, − 1.44 (− 2.10 to − 0.79) for NO2, and − 0.60 (− 1.08, − 0.12) for O3.

Conclusions

Lifestyle partially mediated the association of air pollution with CVD, and adherence to a healthy lifestyle could protect middle-aged and elderly people from the adverse effects of air pollution regarding CVD.
Carbohydrate quality, not quantity, linked to reduced colorectal cancer incidence and mortality in US populations: evidence from a prospective study
Authors: Xiao Yi , Xiang Ling , Jiang Yahui , Tang Yunhao , Gu Haitao , Wang Yaxu , Peng Linglong
Published: March 2024

Background

Carbohydrates have been implicated in colorectal cancer (CRC) risk, but the specific impact of carbohydrate quality and quantity on CRC susceptibility in US populations remains unclear.

Methods

We followed 101,694 participants from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The carbohydrate quality index (CQI) and low-carbohydrate diet score (LCDs) were used to evaluate the daily carbohydrate quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to compute HRs and 95% CIs for incident CRC and related death. Subgroup analyses were conducted to identify potential effect modifiers.

Results

During follow-up, we documented 1085 incident cases of CRC, of whom 311 died from CRC. Individuals in the highest compared with the lowest quartiles of CQI had a lower CRC incidence (Q4 vs Q1: HR 0.80, 95% CI 0.67–0.96, Ptrend = 0.012) and mortality (Q4 vs Q1: HR 0.61, 95% CI 0.44–0.86, Ptrend = 0.004). The inverse association between CQI and CRC risk was observed for distal colon and rectum but not for proximal colon cancer. Regarding mortality, this association was only significant for rectum cancer. Subgroup analyses indicated this inverse association of CQI with CRC risk was only observed in participants with lower LCDs. No significant associations were found between LCDs and CRC incidence or mortality.

Conclusions

Our findings suggest focusing on higher quality, rather than restricting the quantity, of carbohydrate consumption may be an effective approach to reduce the risk of CRC in the US population, particularly for distal colon and rectal cancers.
Development and proof-of-concept demonstration of a clinical metagenomics method for the rapid detection of bloodstream infection
Authors: Moragues-Solanas Lluis , Le-Viet Thanh , McSorley Elinor , Halford Carl , Lockhart Daniel S. , Aydin Alp , Kay Gemma L. , Elumogo Ngozi , Mullen William , O’Grady Justin , Gilmour Matthew W.
Published: March 2024

Background

The timely and accurate diagnosis of bloodstream infection (BSI) is critical for patient management. With longstanding challenges for routine blood culture, metagenomics is a promising approach to rapidly provide sequence-based detection and characterisation of bloodborne bacteria. Long-read sequencing technologies have successfully supported the use of clinical metagenomics for syndromes such as respiratory illness, and modified approaches may address two requisite factors for metagenomics to be used as a BSI diagnostic: depletion of the high level of host DNA to then detect the low abundance of microbes in blood.

Methods

Blood samples from healthy donors were spiked with different concentrations of four prevalent causative species of BSI. All samples were then subjected to a modified saponin-based host DNA depletion protocol and optimised DNA extraction, whole genome amplification and debranching steps in preparation for sequencing, followed by bioinformatical analyses. Two related variants of the protocol are presented: 1mL of blood processed without bacterial enrichment, and 5mL of blood processed following a rapid bacterial enrichment protocol—SepsiPURE.

Results

After first identifying that a large proportion of host mitochondrial DNA remained, the host depletion process was optimised by increasing saponin concentration to 3% and scaling the reaction to allow more sample volume. Compared to non-depleted controls, the 3% saponin-based depletion protocol reduced the presence of host chromosomal and mitochondrial DNA < 106 and < 103 fold respectively. When the modified depletion method was further combined with a rapid bacterial enrichment method (SepsiPURE; with 5mL blood samples) the depletion of mitochondrial DNA improved by a further > 10X while also increasing detectable bacteria by > 10X. Parameters during DNA extraction, whole genome amplification and long-read sequencing were also adjusted, and subsequently amplicons were detected for each input bacterial species at each of the spiked concentrations, ranging from 50–100 colony forming units (CFU)/mL to 1–5 CFU/mL.

Conclusion

In this proof-of-concept study, four prevalent BSI causative species were detected in under 12 h to species level (with antimicrobial resistance determinants) at concentrations relevant to clinical blood samples. The use of a rapid and precise metagenomic protocols has the potential to advance the diagnosis of BSI.
Integration analysis of lncRNA and mRNA expression data identifies DOCK4 as a potential biomarker for elderly osteoporosis
Authors: Wu Chengai , Wang Chao , Xiao Bin , Li Shan , Sheng Yueyang , Wang Qianqian , Tao Jianfeng , Zhang Yanzhuo , Jiang Xu
Published: March 2024

Background

We aimed to identify some potential biomarkers for elderly osteoporosis (OP) by integral analysis of lncRNA and mRNA expression data.

Methods

A total of 8 OP cases and 5 healthy participants were included in the study. Fasting peripheral venous blood samples were collected from individuals, and total RNA was extracted. RNA-seq library was prepared and sequenced on the Illumina HiSeq platform. Differential gene expression analysis was performed using “DESeq2” package in R language. Functional enrichment analysis was conducted using the “clusterProfiler” package, and the cis- and trans-regulatory relationships between lncRNA and target mRNA were analyzed by the lncTar software. A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified through the MCODE plugin in Cytoscape.

Results

We identified 897 differentially expressed lncRNAs (DELs) and 1366 differentially expressed genes (DEGs) between normal and OP samples. After co-expression network analysis and cis-trans regulatory genes analysis, we identified 69 candidate genes regulated by lncRNAs. Then we further screened 7 genes after PPI analysis. The target gene DOCK4, trans-regulated by two lncRNAs, was found to be significantly upregulated in OP samples. Additionally, 4 miRNAs were identified as potential regulators of DOCK4. The potential diagnostic value of DOCK4 and its two trans-regulatory lncRNAs was supported by ROC analysis, indicating their potential as biomarkers for OP.

Conclusion

DOCK4 is a potential biomarker for elderly osteoporosis diagnostic. It is identified to be regulated by two lncRNAs and four miRNAs.
Mitochondrial respiratory chain component NDUFA4: a promising therapeutic target for gastrointestinal cancer
Authors: Zhou Quanling , Li Xiaohui , Zhou Honglian , Zhao Juanjuan , Zhao Hailong , Li Lijuan , Zhou Ya
Published: March 2024

Gastrointestinal cancer, one of the most common cancers, continues to be a major cause of mortality and morbidity globally. Accumulating evidence has shown that alterations in mitochondrial energy metabolism are involved in developing various clinical diseases. NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4), encoded by the NDUFA4 gene located on human chromosome 7p21.3, is a component of mitochondrial respiratory chain complex IV and integral to mitochondrial energy metabolism. Recent researchers have disclosed that NDUFA4 is implicated in the pathogenesis of various diseases, including gastrointestinal cancer. Aberrant expression of NDUFA4 leads to the alteration in mitochondrial energy metabolism, thereby regulating the growth and metastasis of cancer cells, indicating that it might be a new promising target for cancer intervention. This article comprehensively reviews the structure, regulatory mechanism, and biological function of NDUFA4. Of note, the expression and roles of NDUFA4 in gastrointestinal cancer including colorectal cancer, liver cancer, gastric cancer, and so on were discussed. Finally, the existing problems of NDUFA4-based intervention on gastrointestinal cancer are discussed to provide help to strengthen the understanding of the carcinogenesis of gastrointestinal cancer, as well as the development of new strategies for clinical intervention.
Evaluating the performance of Plasmodium falciparum genetic metrics for inferring National Malaria Control Programme reported incidence in Senegal
Authors: Wong Wesley , Schaffner Stephen F. , Thwing Julie , Seck Mame Cheikh , Gomis Jules , Diedhiou Younouss , Sy Ngayo , Ndiop Medoune , Ba Fatou , Diallo Ibrahima , Sene Doudou , Diallo Mamadou Alpha , Ndiaye Yaye Die , Sy Mouhamad , Sene Aita , Sow Djiby , Dieye Baba , Tine Abdoulaye , Ribado Jessica , Suresh Joshua , Lee Albert , Battle Katherine E. , Proctor Joshua L. , Bever Caitlin A. , MacInnis Bronwyn , Ndiaye Daouda , Hartl Daniel L. , Wirth Dyann F. , Volkman Sarah K.
Published: March 2024

Background

Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence.

Methods

This study examined parasites from 3147 clinical infections sampled between the years 2012–2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, a series of Poisson generalized linear mixed-effects models were constructed to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates.

Results

Model-predicted incidence was compared with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (< 10/1000/annual [‰]).

Conclusions

When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence > 10‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was < 10‰, many of the correlations between parasite genetics and incidence were reversed, which may reflect the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.
Spike structure of gold nanobranches induces hepatotoxicity in mouse hepatocyte organoid models
Authors: Zhang Rui , Li Dan , Zhao Ruibo , Luo Dandan , Hu Yeting , Wang Shengyan , Zhuo Xiaolu , Iqbal M. Zubair , Zhang Han , Han Qianqian , Kong Xiangdong
Published: March 2024

Background

Gold nanoparticles (GNPs) have been extensively recognized as an active candidate for a large variety of biomedical applications. However, the clinical conversion of specific types of GNPs has been hindered due to their potential liver toxicity. The origin of their hepatotoxicity and the underlying key factors are still ambiguous. Because the size, shape, and surfactant of GNPs all affect their properties and cytotoxicity. An effective and sensitive platform that can provide deep insights into the cause of GNPs’ hepatotoxicity in vitro is therefore highly desired.

Methods

Here, hepatocyte organoid models (Hep-orgs) were constructed to evaluate the shape-dependent hepatotoxicity of GNPs. Two types of GNPs with different nanomorphology, gold nanospheres (GNSs) and spiny gold nanobranches (GNBs), were synthesized as the representative samples. Their shape-dependent effects on mice Hep-orgs’ morphology, cellular cytoskeletal structure, mitochondrial structure, oxidative stress, and metabolism were carefully investigated.

Results

The results showed that GNBs with higher spikiness and tip curvature exhibited more significant cytotoxicity compared to the rounded GNSs. The spike structure of GNBs leads to a mitochondrial damage, oxidative stress, and metabolic disorder in Hep-orgs. Meanwhile, similar trends can be observed in HepG2 cells and mice models, demonstrating the reliability of the Hep-orgs.

Conclusions

Hep-orgs can serve as an effective platform for exploring the interactions between GNPs and liver cells in a 3D perspective, filling the gap between 2D cell models and animal models. This work further revealed that organoids can be used as an indispensable tool to rapidly screen and explore the toxic mechanism of nanomaterials before considering their biomedical functionalities.
Framework for policymaking on self-management of health by older adults using technologies
Authors: Gauthier-Beaupré Amélie , Kuziemsky Craig , Battistini Bruno J. , Jutai Jeffrey W.
Published: March 2024

Background

During the coronavirus disease 2019 (COVID-19) pandemic, the use of information and communication technologies (ICTs) to support care management exponentially increased. Governments around the world adapted existing programs to meet the needs of patients. The reactivity of governments, however, led to changes that were inequitable, undermining groups such as older adults living with chronic diseases and disability. Policies that align with recent developments in ICTs can promote better health outcomes and innovation in care management. A framework for policymaking presents potential for overcoming barriers and gaps that exist in current policies.

Objective

The goal of this study was to examine how well a provisional framework for policymaking represented the interactions between various components of government policymaking on older adults’ self-management of chronic disease and disability using ICTs.

Methods

Through an online survey, the study engaged policymakers from various ministries of the government of Ontario in the evaluation and revision of the framework. The data were analyzed using simple statistics and by interpreting written comments.

Results

Nine participants from three ministries in the government of Ontario responded to the questionnaire. Overall, participants described the framework as useful and identified areas for improvement and further clarification. A revised version of the framework is presented.

Conclusions

Through the revision exercise, our study confirmed the relevance and usefulness for a policymaking framework on the self-management of disease and disability of older adults’ using ICTs. Further inquiries should examine the application of the framework to jurisdictions other than Ontario considering the dissociated nature of Canadian provincial healthcare systems.
Effects of combined dietary intervention and physical-cognitive exercise on cognitive function and cardiometabolic health of postmenopausal women with obesity: a randomized controlled trial
Authors: Keawtep Puntarik , Sungkarat Somporn , Boripuntakul Sirinun , Sa-nguanmoo Piangkwan , Wichayanrat Wanachaporn , Chattipakorn Siriporn C. , Worakul Puangsoi
Published: March 2024

Background

Postmenopausal women with obesity are markedly at risk of cognitive impairment and several health issues. Emerging evidence demonstrated that both diet and exercise, particularly physical-cognitive exercise are involved in cognitive and health benefits. However, the comparative effect of diet, exercise, and combined interventions in postmenopausal women with obesity on cognition and cardiometabolic health is still lacking. Identifying the effective health promotion program and understanding changes in cardiometabolic health linking these interventions to cognition would have important medical implications. This RCT aimed to examine the effect of single and combined interventions of diet and exercise on cognitive function and cardiometabolic health in postmenopausal women with obesity.

Methods

Ninety-two postmenopausal women with obesity were randomly assigned to diet group (intermittent fasting 2 days/week, 3 months), exercise group (physical-cognitive exercise 3 days/week, 3 months), combined group, or control group (n = 23/group). All cognitive outcomes and cardiometabolic outcomes were measured at baseline and post-3 months. Primary outcomes were executive functions, memory, and plasma BDNF levels. Secondary outcomes were global cognition, attention, language domain, plasma adiponectin levels, IL-6 levels, metabolic parameters, and physical function.

Results

At the end of the 3-month intervention, the exercise and combined group demonstrated significant memory improvement which was accompanied by significant improvements in plasma BDNF level, insulin levels, HOMA-IR, %body fat, and muscle strength when compared to controls (p < 0.05). Only the combined intervention group demonstrated a significant improvement in executive function and increased plasma adiponectin levels when compared to control (p < 0.05). Surprisingly, no cognitive improvement was observed in the diet group (p > 0.05). Significant reduction in cholesterol levels was shown in the diet and combined groups when compared to controls (p < 0.05). Among the three intervention groups, there were no significant differences in all cognitive outcomes and cardiometabolic outcomes (p > 0.05). However, all three intervention groups showed significant improvements in plasma BDNF levels, weight, BMI, WHR, fat mass, and predicted VO2 max, when compared to control (p < 0.05).

Conclusion

These findings suggest that combined physical-cognitive exercise and dietary intervention are promising interventions to improve cognition and obesity-related complications of postmenopausal women with obesity.

Trial registration

NCT04768725 (https://clinicaltrials.gov) 24th February 2021.
Sex-related differences in serum biomarker levels predict the activity and efficacy of immune checkpoint inhibitors in advanced melanoma and non-small cell lung cancer patients
Authors: Pasello Giulia , Fabricio Aline S. C. , Del Bianco Paola , Salizzato Valentina , Favaretto Adolfo , Piccin Luisa , Zustovich Fable , Fabozzi Alessio , De Rossi Costanza , Pigozzo Jacopo , De Nuzzo Mattia , Cappelletto Elia , Bonanno Laura , Palleschi Dario , De Salvo Gian Luca , Guarneri Valentina , Gion Massimo , Chiarion-Sileni Vanna
Published: March 2024

Background

Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization.

Methods

In this prospective study, we enrolled immunotherapy-naïve patients affected by advanced MM and NSCLC treated with ICIs. The primary endpoint was to dissect the potential sex correlations between serum cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, MCP-1, TNF-ɑ, IP-10, VEGF, sPD-L1) and the objective response rate (ORR). Secondly, we analyzed biomarker changes during treatment related to ORR, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Blood samples, collected at baseline and during treatment until disease progression (PD) or up to 2 years, were analyzed using Luminex xMAP or ELLA technologies.

Results

Serum samples from 161 patients (98 males/63 females; 92 MM/69 NSCLC) were analyzed for treatment response. At baseline, IL-6 was significantly lower in females (F) versus males (M); lower levels of IL-4 in F and of IL-6 in both sexes significantly correlated with a better ORR, while higher IL-4 and TNF-ɑ values were predictive of a lower ORR in F versus M. One hundred and sixty-five patients were evaluable for survival analysis: at multiple Cox regression, an increased risk of PD was observed in F with higher baseline values of IL-4, sPD-L1 and IL-10, while higher IL-6 was a negative predictor in males. In males, higher levels of GM-CSF predict a longer survival, whereas higher IL-1β predicts a shorter survival. Regardless of sex, high baseline IL-8 values were associated with an increased risk of both PD and death, and high IL-6 levels only with shorter OS.

Conclusions

Serum IL-1β, IL-4, IL-6, IL-10, GM-CSF, TNF-ɑ, and sPD-L1 had a significant sex-related predictive impact on ORR, PFS and OS in melanoma and NSCLC patients treated with ICIs. These results will potentially pave the way for new ICI combinations, designed according to baseline and early changes of these cytokines and stratified by sex.
Integrative analysis of chromatin accessibility and transcriptome landscapes in the induction of peritoneal fibrosis by high glucose
Authors: Song Qiong , Wang Pengbo , Wang Huan , Pan Meijing , Li Xiujuan , Yao Zhuan’e , Wang Wei , Tang Guangbo , Zhou Sen
Published: March 2024

Background

Peritoneal fibrosis is the prevailing complication induced by prolonged exposure to high glucose in patients undergoing peritoneal dialysis.

Methods

To elucidate the molecular mechanisms underlying this process, we conducted an integrated analysis of the transcriptome and chromatin accessibility profiles of human peritoneal mesothelial cells (HMrSV5) during high-glucose treatment.

Results

Our study identified 2775 differentially expressed genes (DEGs) related to high glucose-triggered pathological changes, including 1164 upregulated and 1611 downregulated genes. Genome-wide DEGs and network analysis revealed enrichment in the epithelial–mesenchymal transition (EMT), inflammatory response, hypoxia, and TGF-beta pathways. The enriched genes included VEGFA, HIF-1α, TGF-β1, EGF, TWIST2, and SNAI2. Using ATAC-seq, we identified 942 hyper (higher ATAC-seq signal in high glucose-treated HMrSV5 cells than in control cells) and 714 hypo (lower ATAC-seq signal in high glucose-treated HMrSV5 cells versus control cells) peaks with differential accessibility in high glucose-treated HMrSV5 cells versus controls. These differentially accessible regions were positively correlated (R = 0.934) with the nearest DEGs. These genes were associated with 566 up- and 398 downregulated genes, including SNAI2, TGF-β1, HIF-1α, FGF2, VEGFA, and VEGFC, which are involved in critical pathways identified by transcriptome analysis. Integrated ATAC-seq and RNA-seq analysis also revealed key transcription factors (TFs), such as HIF-1α, ARNTL, ELF1, SMAD3 and XBP1. Importantly, we demonstrated that HIF-1α is involved in the regulation of several key genes associated with EMT and the TGF-beta pathway. Notably, we predicted and experimentally validated that HIF-1α can exacerbate the expression of TGF-β1 in a high glucose-dependent manner, revealing a novel role of HIF-1α in high glucose-induced pathological changes in human peritoneal mesothelial cells (HPMCs).

Conclusions

In summary, our study provides a comprehensive view of the role of transcriptome deregulation and chromosome accessibility alterations in high glucose-induced pathological fibrotic changes in HPMCs. This analysis identified hub genes, signaling pathways, and key transcription factors involved in peritoneal fibrosis and highlighted the novel glucose-dependent regulation of TGF-β1 by HIF-1α. This integrated approach has offered a deeper understanding of the pathogenesis of peritoneal fibrosis and has indicated potential therapeutic targets for intervention.
Rediscovering the unusual, solitary bryozoan Monobryozoon ambulans Remane, 1936: first molecular and new morphological data clarify its phylogenetic position
Authors: Schwaha Thomas , Decker Sebastian H. , Baranyi Christian , Saadi Ahmed J.
Published: March 2024

Background

One of the most peculiar groups of the mostly colonial phylum Bryozoa is the taxon Monobryozoon, whose name already implies non-colonial members of the phylum. Its peculiarity and highly unusual lifestyle as a meiobenthic clade living on sand grains has fascinated many biologists. In particular its systematic relationship to other bryozoans remains a mystery. Despite numerous searches for M. ambulans in its type locality Helgoland, a locality with a long-lasting marine station and tradition of numerous courses and workshops, it has never been reencountered until today. Here we report the first observations of this almost mythical species, Monobryozoon ambulans.

Results

For the first time since 1938, we present new modern, morphological analyses of this species as well as the first ever molecular data. Our detailed morphological analysis confirms most previous descriptions, but also ascertains the presence of special ambulatory polymorphic zooids. We consider these as bud anlagen that ultimately consecutively separate from the animal rendering it pseudo-colonial. The remaining morphological data show strong ties to alcyonidioidean ctenostome bryozoans. Our morphological data is in accordance with the phylogenomic analysis, which clusters it with species of Alcyonidium as a sister group to multiporate ctenostomes. Divergence time estimation and ancestral state reconstruction recover the solitary state of M. ambulans as a derived character that probably evolved in the Late Cretaceous. In this study, we also provide the entire mitogenome of M. ambulans, which—despite the momentary lack of comparable data—provides important data of a unique and rare species for comparative aspects in the future.

Conclusions

We were able to provide first sequence data and modern morphological data for the unique bryozoan, M. ambulans, which are both supporting an alcyonidioidean relationship within ctenostome bryozoans.
Clinical effects of arthroscopic-assisted uni-portal spinal surgery and unilateral bi-portal endoscopy on unilateral laminotomy for bilateral decompression in patients with lumbar spinal stenosis: a retrospective cohort study
Authors: Wang Fang , Wang Rui , Zhang Chengyi , Song En , Li Fengtao
Published: March 2024

Objective

To investigate the clinical effectiveness of Arthroscopic-assisted Uni-portal Spinal Surgery (AUSS) in the treatment of lumbar spinal stenosis.

Methods

A total of 475 patients with lumbar spinal stenosis from January 2019 to January 2023 were included in this study. Among them, 240 patients were treated with AUSS (AUSS group); the other 235 patients were treated with unilateral bi-portal endoscopy treatment (UBE group). The differences in surgery-related clinical indicators, pain degree before and after surgery, Oswestry Disability Index (ODI), CT imaging parameters of spinal stenosis, and clinical efficacy were compared between the two groups.

Results

Patients in the AUSS group had a shorter operative time than those in the UBE group, and the length of incision and surgical bleeding were less than those in the UBE group, with statistically significant differences (P < 0.05). Before operation, there was no significant difference in the VAS score of low back pain and leg pain between the two groups (P > 0. 05). After operation, patients in both groups showed a significant reduction in low back and leg pain, and their VAS scores were significantly lower than before the operation (P < 0.05). Three months after surgery, the results of CT re-examination in both groups showed that the spinal stenosis of the patients was well improved, and the measurements of lumbar spinal interspace APDC, CAC, ICA, CAD and LAC were significantly higher than those before surgery (P < 0. 05). Besides, the lumbar function of patients improved significantly in both groups, and ODI measurements were significantly lower than those before surgery (P < 0.05).

Conclusion

Both AUSS and UBE with unilateral laminotomy for bilateral decompression can achieve good clinical results in the treatment of lumbar spinal stenosis, but the former has the advantages of simpler operation, shorter operation time, shorter incision length, and less surgical blood loss.
Toxicities, intensive care management, and outcome of chimeric antigen receptor T cells in adults: an update
Authors: Bellal Mathieu , Malherbe Jolan , Damaj Gandhi , Du Cheyron Damien
Published: March 2024

Background

Chimeric antigen receptor T cells are a promising new immunotherapy for haematological malignancies. Six CAR-T cells products are currently available for adult patients with refractory or relapsed high-grade B cell malignancies, but they are associated with severe life-threatening toxicities and side effects that may require admission to ICU.

Objective

The aim of this short pragmatic review is to synthesize for intensivists the knowledge on CAR-T cell therapy with emphasis on CAR-T cell-induced toxicities and ICU management of complications according to international recommendations, outcomes and future issues.

Graphical abstract
Peutz–Jeghers syndrome with polyps in the stomach, duodenum, and small and large intestine: a case report
Authors: Shah Zaryab Ali , Zeb Muhammad , Ilyas Muhammad , Hamid Hasnain , Fatima Komal , Batool Maria , Abbas Muhammad
Published: March 2024

Background

Peutz–Jeghers syndrome is a rare hereditary condition characterized by gastrointestinal polyps and pigmented oral lesions. The case contributes to a deeper understanding of Peutz–Jeghers syndrome and underscores the significance of interdisciplinary collaboration for accurate diagnosis and tailored therapeutic strategies.

Case description

We present a case of a 15-year-old Afghan female patient with multiple polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. Despite previous medical visits and colonoscopies, her symptoms persisted. A multidisciplinary team discussed the case and recommended further investigations and interventions. A polypectomy was performed, confirming the presence of hamartomatous polyps. The patient was diagnosed with Peutz–Jeghers syndrome, but during the course of treatment she went through complications and was managed surgically as well.

Conclusion

Timely polyp removal and lifelong surveillance are crucial in managing Peutz–Jeghers syndrome. Further research and genetic analysis are needed to improve understanding and management of this rare disorder.
Impacts of priming on distinct immunosuppressive mechanisms of mesenchymal stromal cells under translationally relevant conditions
Authors: Herger Nick , Heggli Irina , Mengis Tamara , Devan Jan , Arpesella Leonardo , Brunner Florian , Distler Oliver , Dudli Stefan
Published: March 2024

Background

The multimodal properties of mesenchymal stromal cells (MSCs), particularly their ability to modulate immune responses is of high interest in translational research. Pro-inflammatory, hypoxic, and 3D culture priming are promising and often used strategies to improve the immunosuppressive potency of MSCs, but the underlying mechanisms are not well understood. Therefore, the aims of this study were (i) to compare the effects of pro-inflammatory, hypoxic, and 3D culture priming on the in vitro immunosuppressive potential of MSCs, (ii) to assess if immunosuppressive priming effects are temporally preserved under standard and translationally relevant culture conditions, and (iii) to investigate if the three priming strategies engage the same immunosuppressive mechanisms.

Methods

Functional in vitro T cell suppressive potency measurements were conducted to assess the impact of pro-inflammatory, hypoxic, and 3D culture priming on the immunosuppressive potential of human bone marrow-derived MSCs. Primed MSCs were either cultured under standard cell culture conditions or translationally relevant culture conditions, and their transcriptomic adaptations were monitored over time. Next-generation sequencing was performed to assess if different priming strategies activate distinct immunosuppressive mechanisms.

Results

(i) Pro-inflammatory, hypoxic, and 3D culture priming induced profound transcriptomic changes in MSCs resulting in a significantly enhanced T cell suppressive potential of pro-inflammatory and 3D culture primed MSCs. (ii) Priming effects rapidly faded under standard cell culture conditions but were partially preserved under translationally relevant conditions. Interestingly, continuous 3D culture priming of MSCs maintained the immunosuppressive potency of MSCs. (iii) Next-generation sequencing revealed that priming strategy-specific differentially expressed genes are involved in the T cell suppressive capacity of MSCs, indicating that different priming strategies engage distinct immunosuppressive mechanisms.

Conclusion

Priming can be a useful approach to improve the immunosuppressive potency of MSCs. However, future studies involving primed MSCs should carefully consider the significant impact of translationally relevant conditions on the preservation of priming effects. Continuous 3D culture could act as a functionalized formulation, supporting the administration of MSC spheroids for a sustainably improved immunosuppressive potency.
Non-cytopathic bovine viral diarrhea virus (BVDV) inhibits innate immune responses via induction of mitophagy
Authors: Li Zhijun , Zhang Ying , Zhao Bao , Xue Qinghong , Wang Chunjiang , Wan Siyu , Wang Jingyu , Chen Xiwen , Qi Xuefeng
Published: March 2024

Bovine viral diarrhea virus (BVDV) belongs to the genus Pestivirus within the family Flaviviridae. Mitophagy plays important roles in virus-host interactions. Here, we provide evidence that non-cytopathic (NCP) BVDV shifts the balance of mitochondrial dynamics toward fission and induces mitophagy to inhibit innate immune responses. Mechanistically, NCP BVDV triggers the translocation of dynamin-related protein (Drp1) to mitochondria and stimulates its phosphorylation at Ser616, leading to mitochondrial fission. In parallel, NCP BVDV-induced complete mitophagy via Parkin-dependent pathway contributes to eliminating damaged mitochondria to inhibit MAVS- and mtDNA-cGAS-mediated innate immunity responses, mtROS-mediated inflammatory responses and apoptosis initiation. Importantly, we demonstrate that the LIR motif of ERNS is essential for mitophagy induction. In conclusion, this study is the first to show that NCP BVDV-induced mitophagy plays a central role in promoting cell survival and inhibiting innate immune responses in vitro.
Pulmonary function testing in preoperative high-risk patients
Authors: Eimer Christine , Urbaniak Natalia , Dempfle Astrid , Becher Tobias , Schädler Dirk , Weiler Norbert , Frerichs Inéz
Published: March 2024

Background

Postoperative respiratory failure is the most frequent complication in postsurgical patients. The purpose of this study is to assess whether pulmonary function testing in high-risk patients during preoperative assessment detects previously unknown respiratory impairments which may influence patient outcomes.

Methods

A targeted patient screening by spirometry and the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) was implemented in the anesthesia department of a tertiary university hospital. Patients of all surgical disciplines who were at least 75 years old or exhibited reduced exercise tolerance with the metabolic equivalent of task less than four (MET < 4) were examined. Clinical characteristics, history of lung diseases, and smoking status were also recorded. The statistical analysis entailed t-tests, one-way ANOVA, and multiple linear regression with backward elimination for group comparisons.

Results

Among 256 included patients, 230 fulfilled the test quality criteria. Eighty-one (35.2%) patients presented obstructive ventilatory disorders, out of which 65 were previously unknown. 38 of the newly diagnosed obstructive disorders were mild, 18 moderate, and 9 severe. One hundred forty-five DLCO measurements revealed 40 (27.6%) previously unknown gas exchange impairments; 21 were mild, 17 moderate, and 2 severe. The pulmonary function parameters of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly lower than the international reference values of a healthy population. Patients with a lower ASA class and no history of smoking exhibited higher FVC, FEV1, and DLCO values. Reduced exercise tolerance with MET < 4 was strongly associated with lower spirometry values.

Conclusions

Our screening program detected a relevant number of patients with previously unknown obstructive ventilatory disorders and impaired pulmonary gas exchange. This newly discovered sickness is associated with low metabolic equivalents and may influence perioperative outcomes. Whether optimized management of patients with previously unknown impaired lung function leads to a better outcome should be evaluated in multicenter studies.

Trial registration

German Registry of Clinical Studies (DRKS00029337), registered on: June 22nd, 2022.
Mom, dad, put down your phone and talk to me: how parental phubbing influences problematic internet use among adolescents
Authors: Liu Saifang , Wu Peiqian , Han Xiaoxi , Wang Mengyun , Kan Yuecui , Qin Kuiyuan , Lan Jijun
Published: March 2024

Background

The positive association of parental phubbing with internalising and externalising problems among adolescents has gained academic traction. To date, limited research has investigated the association of parental phubbing and adolescents’ Problematic Internet Use (PIU). Furthermore, the mechanism underlying this association is largely unknown. These gaps limit our understanding of family-related issues affecting PIU among adolescents. The present study explores whether there is a relation between parental phubbing and PIU and investigates the mechanisms underlying this relation among adolescents.

Methods

The participants were 495 junior high schoolers aged 11–15 years. Participants completed questionnaires on their experiences with PIU, parental phubbing, parent–child relationships, and basic psychological needs satisfaction.

Results

The results showed a direct and indirect positive association between parental phubbing and PIU. Furthermore, parental phubbing indirectly influenced PIU and was mediated by the parent–child relationship and basic psychological needs satisfaction, respectively. Moreover, the parent–child relationship and basic psychological needs satisfaction were sequentially mediated.

Conclusions

Our study highlights the crucial role of parents in the development of adolescent PIU and provides theoretical and practical guidelines for PIU prevention and intervention.