bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity of food and nutrient intakes assessed by a food frequency questionnaire among Chinese adults
Authors: Zhao Dong , Gong Yiying , Huang Liyan , Lv Rongxia , Gu Yuxuan , Ni Chunxiao , Zhu Dafang , Yang Min , Rong Shuang , Zhang Ronghua , Yuan Changzheng
Published: February 2024

Background

Studies regarding the validity of the food frequency questionnaire (FFQ) and the food composition table (FCT) are limited in Asian countries. We aimed to evaluate the validity of a 64-item FFQ and different methods of constructing the FFQ FCTs for assessing dietary intakes of foods and nutrients among adults in eastern China.

Methods

A total of 2325 participants (aged 56.2 ± 14.9 years, 51.6% female) from nine cities in Zhejiang province who completed a 64-item FFQ and 3-day 24-hour dietary recalls (24HRs) in 2015 were included. Eight FFQ FCTs were generated covering food items and specific weights estimated using professional knowledge, representative 24HRs data, or the Chinese FCT (CFCT). Energy-adjusted intakes of foods and nutrients were estimated by residual and energy density methods. Spearman correlation coefficients (SCCs) of intakes of 14 food groups and 17 nutrients between FFQ and 24HRs were calculated to evaluate the overall validity of FFQ.

Results

The average intakes of most food groups and nutrients assessed with FFQ were higher than those assessed using the 24HRs. For the food groups, the averaged energy-adjusted (residual method) SCC between FFQ and 24HRs was 0.27, ranging from 0.14 (starch-rich beans) to 0.49 (aquatic products). For nutrient assessment, the weighted FCT (WFCT) performs the best, and the averaged energy-adjusted (residual method) SCC was 0.26, ranging from 0.16 (iron) to 0.37 (potassium). Similar correlations with 24HRs were observed when using other FFQ FCT in the calculation of nutrient intakes.

Conclusion

The 64-item Chinese FFQ and the WFCT were reasonably valid to assess the dietary intakes of certain foods and nutrients among adults in eastern China.
Hauora Māori – Māori health: a right to equal outcomes in primary care
Authors: Sheridan Nicolette , Jansen Rawiri McKree , Harwood Matire , Love Tom , Kenealy Timothy ,   The Primary Care Models Study Group, Aguirre-Duarte Nelson , Arroll Bruce , Atmore Carol , Carryer Jenny , Crampton Peter , Dowell Anthony , Fishman Tana , Gauld Robin , Hoare Karen , Jackson Gary , Kerse Ngaire , Lampshire Debra , McBain Lynn , MacRae Jayden , Mills Jane , Øvretveit John , Percival Teuila , Perera Roshan , Roland Martin , Ryan Debbie , Schmidt-Busby Jacqueline , Stokes Tim , Stubbe Maria
Published: February 2024

Background

For more than a century, Māori have experienced poorer health than non-Māori. In 2019 an independent Tribunal found the Government had breached Te Tiriti o Waitangi by “failing to design and administer the current primary health care system to actively address persistent Māori health inequities”. Many Māori (44%) have unmet needs for primary care. Seven models of primary care were identified by the funders and the research team, including Māori-owned practices. We hypothesised patient health outcomes for Māori would differ between models of care.

Methods

Cross-sectional primary care data were analysed at 30 September 2018. National datasets were linked to general practices at patient level, to measure associations between practice characteristics and patient health outcomes. Primary outcomes: polypharmacy (≥ 55 years), HbA1c testing, child immunisations, ambulatory sensitive hospitalisations (0–14, 45–64 years) and emergency department attendances. Regressions include only Māori patients, across all models of care.

Results

A total of 660,752 Māori patients were enrolled in 924 practices with 124,854 in 65 Māori-owned practices.

Māori practices had: no significant association with HbA1c testing, ambulatory sensitive hospitalisations or ED attendances, and a significant association with lower polypharmacy (3.7% points) and lower childhood immunisations (13.4% points).

Māori practices had higher rates of cervical smear and cardiovascular risk assessment, lower rates of HbA1c tests, and more nurse (46%) and doctor (8%) time (FTE) with patients.

The average Māori practice had 52% Māori patients compared to 12% across all practices. Māori practices enrolled a higher percentage of children and young people, five times more patients in high deprivation areas, and patients with more multimorbidity.

More Māori patients lived rurally (21.5% vs 15%), with a greater distance to the nearest ED. Māori patients were more likely to be dispensed antibiotics or tramadol.

Conclusions

Māori practices are an expression of autonomy in the face of enduring health system failure. Apart from lower immunisation rates, health outcomes were not different from other models of care, despite patients having higher health risk profiles. Across all models, primary care need was unmet for many Māori, despite increased clinical input. Funding must support under-resourced Māori practices and ensure accountability for the health outcomes of Māori patients in all models of general practice.
Inhalable hybrid nanovaccines with virus-biomimetic structure boost protective immune responses against SARS-CoV-2 variants
Authors: Wang Shuqi , Ding Peiyang , Shen Lingli , Fan Daopeng , Cheng Hanghang , Huo Jian , Wei Xin , He Hua , Zhang Gaiping
Published: February 2024

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with different antigenic variants, has posed a significant threat to public health. It is urgent to develop inhalable vaccines, instead of injectable vaccines, to elicit mucosal immunity against respiratory viral infections.

Methods

We reported an inhalable hybrid nanovaccine (NVRBD-MLipo) to boost protective immunity against SARS-CoV-2 infection. Nanovesicles derived from genetically engineered 293T cells expressing RBD (NVRBD) were fused with pulmonary surfactant (PS)-biomimetic liposomes containing MPLA (MLipo) to yield NVRBD-MLipo, which possessed virus-biomimetic structure, inherited RBD expression and versatile properties.

Results

In contrast to subcutaneous vaccination, NVRBD-MLipo, via inhalable vaccination, could efficiently enter the alveolar macrophages (AMs) to elicit AMs activation through MPLA-activated TLR4/NF-κB signaling pathway. Moreover, NVRBD-MLipo induced T and B cells activation, and high level of RBD-specific IgG and secretory IgA (sIgA), thus elevating protective mucosal and systemic immune responses, while reducing side effects. NVRBD-MLipo also demonstrated broad-spectrum neutralization activity against SARS-CoV-2 (WT, Delta, Omicron) pseudovirus, and protected immunized mice against WT pseudovirus infection.

Conclusions

This inhalable NVRBD-MLipo, as an effective and safe nanovaccine, holds huge potential to provoke robust mucosal immunity, and might be a promising vaccine candidate to combat respiratory infectious diseases, including COVID-19 and influenza.
KIT mutations and expression: current knowledge and new insights for overcoming IM resistance in GIST
Authors: Zhou Shishan , Abdihamid Omar , Tan Fengbo , Zhou Haiyan , Liu Heli , Li Zhi , Xiao Sheng , Li Bin
Published: February 2024

Gastrointestinal stromal tumor (GIST) is the most common sarcoma located in gastrointestinal tract and derived from the interstitial cell of Cajal (ICC) lineage. Both ICC and GIST cells highly rely on KIT signal pathway. Clinically, about 80-90% of treatment-naive GIST patients harbor primary KIT mutations, and special KIT-targeted TKI, imatinib (IM) showing dramatic efficacy but resistance invariably occur, 90% of them was due to the second resistance mutations emerging within the KIT gene. Although there are multiple variants of KIT mutant which did not show complete uniform biologic characteristics, most of them have high KIT expression level. Notably, the high expression level of KIT gene is not correlated to its gene amplification. Recently, accumulating evidences strongly indicated that the gene coding, epigenetic regulation, and pre- or post- protein translation of KIT mutants in GIST were quite different from that of wild type (WT) KIT. In this review, we elucidate the biologic mechanism of KIT variants and update the underlying mechanism of the expression of KIT gene, which are exclusively regulated in GIST, providing a promising yet evidence-based therapeutic landscape and possible target for the conquer of IM resistance.
Emerging roles of circular RNAs in tumorigenesis, progression, and treatment of gastric cancer
Authors: Ma Qiang , Yang Feifei , Xiao Bin , Guo Xiaolan
Published: February 2024

With an estimated one million new cases reported annually, gastric cancer (GC) ranks as the fifth most diagnosed malignancy worldwide. The early detection of GC remains a major challenge, and the prognosis worsens either when patients develop resistance to chemotherapy or radiotherapy or when the cancer metastasizes. The precise pathogenesis underlying GC is not well understood, which further complicates its treatment. Circular RNAs (circRNAs), a recently discovered class of noncoding RNAs that originate from parental genes through “back-splicing”, have been shown to play a key role in various biological processes in both eukaryotes and prokaryotes. CircRNAs have been linked to cardiovascular diseases, diabetes, hypertension, Alzheimer's disease, and the occurrence and progression of tumors. Prior studies have established that circRNAs play a crucial role in GC, impacting tumorigenesis, diagnosis, progression, and therapy resistance. This review aims to summarize how circRNAs contribute to GC tumorigenesis and progression, examine their roles in the development of drug resistance, discuss their potential as biotechnological drugs, and summarize their response to therapeutic drugs and microorganism in GC.
Targeting of mitochondrial fission through natural flavanones elicits anti-myeloma activity
Authors: Torcasio Roberta , Gallo Cantafio Maria Eugenia , Veneziano Claudia , De Marco Carmela , Ganino Ludovica , Valentino Ilenia , Occhiuzzi Maria Antonietta , Perrotta Ida Daniela , Mancuso Teresa , Conforti Filomena , Rizzuti Bruno , Martino Enrica Antonia , Gentile Massimo , Neri Antonino , Viglietto Giuseppe , Grande Fedora , Amodio Nicola
Published: February 2024

Background

Mitochondrial alterations, often dependent on unbalanced mitochondrial dynamics, feature in the pathobiology of human cancers, including multiple myeloma (MM). Flavanones are natural flavonoids endowed with mitochondrial targeting activities. Herein, we investigated the capability of Hesperetin (Hes) and Naringenin (Nar), two aglycones of Hesperidin and Naringin flavanone glycosides, to selectively target Drp1, a pivotal regulator of mitochondrial dynamics, prompting anti-MM activity.

Methods

Molecular docking analyses were performed on the crystallographic structure of Dynamin-1-like protein (Drp1), using Hes and Nar molecular structures. Cell viability and apoptosis were assessed in MM cell lines, or in co-culture systems with primary bone marrow stromal cells, using Cell Titer Glo and Annexin V-7AAD staining, respectively; clonogenicity was determined using methylcellulose colony assays. Transcriptomic analyses were carried out using the Ion AmpliSeq™ platform; mRNA and protein expression levels were determined by quantitative RT-PCR and western blotting, respectively. Mitochondrial architecture was assessed by transmission electron microscopy. Real time measurement of oxygen consumption was performed by high resolution respirometry in living cells. In vivo anti-tumor activity was evaluated in NOD-SCID mice subcutaneously engrafted with MM cells.

Results

Hes and Nar were found to accommodate within the GTPase binding site of Drp1, and to inhibit Drp1 expression and activity, leading to hyperfused mitochondria with reduced OXPHOS. In vitro, Hes and Nar reduced MM clonogenicity and viability, even in the presence of patient-derived bone marrow stromal cells, triggering ER stress and apoptosis. Interestingly, Hes and Nar rewired MM cell metabolism through the down-regulation of master transcriptional activators (SREBF-1, c-MYC) of lipogenesis genes. An extract of Tacle, a Citrus variety rich in Hesperidin and Naringin, was capable to recapitulate the phenotypic and molecular perturbations of each flavanone, triggering anti-MM activity in vivo.

Conclusion

Hes and Nar inhibit proliferation, rewire the metabolism and induce apoptosis of MM cells via antagonism of the mitochondrial fission driver Drp1. These results provide a framework for the development of natural anti-MM therapeutics targeting aberrant mitochondrial dependencies.
Trends in orphan medicinal products approvals in the European Union between 2010–2022
Authors: Bouwman Luísa , Sepodes Bruno , Leufkens Hubert , Torre Carla
Published: February 2024

Background

Over the last twenty years of orphan drug regulation in Europe, the regulatory framework has increased its complexity, with different regulatory paths and tools engineered to facilitate the innovation and accelerate approvals. Recently, the proposal of the new Pharmaceutical Legislation for the European Union, which will replace at least three Regulations and one Directive, was released and its new framework is raising many questions. The aim of this study was to present a characterisation of the Orphan Medicinal Products (OMPs) authorised by the European Commission (EC), between 2010 and 2022, looking into eighteen variables, contributing to the ongoing discussion on the proposal and implementation of the new Pharmaceutical Legislation proposed.

Methods

Data of the OMPs identified and approved between 2010 and 2022 were extracted from the European Public Assessment Reports (EPARs) produced by the European Medicines Agency. Information regarding legal basis of the application, applicant, protocol assistance received, type of authorization, registration status, type of molecule, ATC code, therapeutic area, target age, disease prevalence, number of pivotal clinical trials supporting the application, clinical trial designs, respective efficacy endpoints and number of patients enrolled in the pivotal clinical trials were extracted. A descriptive statistical analysis was applied.

Results

We identified 192 OMPs approved in the period between 2010 and 2022. 89% of the OMPs have legal basis of “full application”. 86% of the sponsors received protocol assistance whereas 64% of the MAA benefited from the accelerated assessment. 53% of the active substances are small molecules; about 1 in 5 molecules are repurposed. 40% of the OMPs have oncological therapeutic indications and 56% of the OMPs are intended to treat only adults. 71% of the products were approved based on a single pivotal trial.

Conclusions

This analysis of OMPs approved between 2010 and 2022 shows that a shift has occurred in the rare disease medicine development space. Through the period studied we observe an increase of non-small molecules approved, accelerated assessment received and non-standard MA’s granted.
The long-term neurodevelopmental outcomes of toddlers with SARS-CoV-2 infection in the neonatal period: a prospective observational study
Authors: Yangin Ergon Ezgi , Alkan Ozdemir Senem , Akbay Ak Sinem , Yenilmez Meltem , Soysal Buse , Kalkanlı Oğuz Han , Çalkavur Şebnem , Gokmen Yıldırım Tülin
Published: February 2024

Background

The effect of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus in the neonatal period on developing brain is still unknown. This study aims to investigate the long-term neurodevelopmental outcomes of newborns exposed to SARS-CoV-2 & Delta variant.

Methods

At a tertiary referral center, a prospective observational cohort research was carried out. All babies who were equal to or more than 34 gestational weeks gestation and were admitted to the NICU between January 2021 and January 2022 due to SARS-CoV-2 infection (Delta - or Delta +) were included in the study. Infants who were hospitalized for non-SARS-CoV-2 reasons at similar dates and who had no history of invasive mechanical ventilation were incorporated as a control group using a 2:1 gender and gestational age match. Thirty infants were assigned to the study group and sixty newborns to the control group based on the sample size calculation. These toddlers’ neurodevelopment was evaluated between the ages of 18 and 24 months using the Bayley-II scale.

Results

We enrolled 90 infants. SARS-CoV-2-positive infants had poorer psychomotor development index (PDI) scores and significantly greater mildly delayed performances (MDPs) at 18–24 months (PDI p = 0.05, MDPs p = 0.03, respectively). Delta variant showed statistically significant lower MDI and PDI scores (MDI p=0.03, PDI p=0.03, respectively). A smaller head circumference of SARS-CoV-2-positive toddlers was detected in the first year (p < 0.001), which improved at the second age.

Conclusion

SARS-CoV-2-positive neonates revealed lower PDI scores and greater MDPs at 18th-24th months. The effect is most noticeable in Delta variant. Longer-term examination of neurodevelopmental outcomes and reevaluation of these children between the ages of 5 and 12 are critical.
Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia
Authors: Lee Chel Hee , Banoei Mohammad M. , Ansari Mariam , Cheng Matthew P. , Lamontagne Francois , Griesdale Donald , Lasry David E. , Demir Koray , Dhingra Vinay , Tran Karen C. , Lee Terry , Burns Kevin , Sweet David , Marshall John , Slutsky Arthur , Murthy Srinivas , Singer Joel , Patrick David M. , Lee Todd C. , Boyd John H. , Walley Keith R. , Fowler Robert , Haljan Greg , Vinh Donald C. , Mcgeer Alison , Maslove David , Mann Puneet , Donohoe Kathryn , Hernandez Geraldine , Rocheleau Genevieve , Trahtemberg Uriel , Kumar Anand , Lou Ma , dos Santos Claudia , Baker Andrew , Russell James A. , Winston Brent W. ,   for the *ARBs CORONA I. Investigators, Russell J. A. , Walley K. R. , Boyd J. , Lee T. , Singer J. , Sweet D. , Tran K. , Reynolds S. , Haljan G. , Cheng M. , Vinh D. , Lee T. , Lamontagne F. , Winston B. , Rewa O. , Marshall J. , Slutsky A. , McGeer A. , Sivanantham V. , Fowler R. , Maslove D. , Patrigeon S. Perez , Burns K. D.
Published: February 2024

Rationale

Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair.

Objective

To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis.

Methods

We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC–MS/MS and DI-MS/MS analytical platforms.

Results

Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms.

Conclusion

Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.
Community composition of black flies during and after the 2020 vesicular stomatitis virus outbreak in Southern New Mexico, USA
Authors: Whelpley Madelin J. , Zhou Lawrence H. , Rascon Jeremy , Payne Bailey , Moehn Brett , Young Katherine I. , Mire Chad E. , Peters Debra P. C. , Rodriguez Luis L. , Hanley Kathryn A.
Published: February 2024

Background

Vesicular stomatitis virus (VSV), a vector-borne pathogen of livestock, emerges periodically in the western US. In New Mexico (NM), US, most cases occur close to the Rio Grande River, implicating black flies (Simulium spp.) as a possible vector. In 2020, VS cases were reported in NM from April to May, although total black fly abundance remained high until September. We investigated the hypothesis that transience of local VSV transmission results from transient abundance of key, competent black fly species. Additionally, we investigated whether irrigation canals in southern NM support a different community of black flies than the main river. Lastly, to gain insight into the source of local black flies, in 2023 we collected black fly larvae prior to the release of water into the Rio Grande River channel.

Methods

We randomly sub-sampled adult black flies collected along the Rio Grande during and after the 2020 VSV outbreak. We also collected black fly adults along the river in 2021 and 2022 and at southern NM farms and irrigation canals in 2022. Black fly larvae were collected from dams in the area in 2023. All collections were counted, and individual specimens were subjected to molecular barcoding for species identification.

Results

DNA barcoding of adult black flies detected four species in 2020: Simulium meridionale (N = 158), S. mediovittatum (N = 83), S. robynae (N = 26) and S. griseum/notatum (N = 1). Simulium robynae was only detected during the VSV outbreak period, S. meridionale showed higher relative abundance, but lower absolute abundance, during the outbreak than post-outbreak period, and S. mediovittatum was rare during the outbreak period but predominated later in the summer. In 2022, relative abundance of black fly species did not differ significantly between the Rio Grande sites and farm and irrigation canals. Intriguingly, 63 larval black flies comprised 56% Simulium vittatum, 43% S. argus and 1% S. encisoi species that were either extremely rare or not detected in previous adult collections.

Conclusions

Our results suggest that S. robynae and S. meridionale could be shaping patterns of VSV transmission in southern NM. Thus, field studies of the source of these species as well as vector competence studies are warranted.

Graphical Abstract
An integrated data analysis reveals distribution, hosts, and pathogen diversity of Haemaphysalis concinna
Authors: Liu Jing , Han Xiao-Yu , Ye Run-Ze , Xu Qing , Wang Xiao-Yang , Li Ze-Hui , Sun Yi , Song Ke , Wang Bao-Yu , Wang Shan-Shan , Liu Jin-Yue , Zhao Lin , Cao Wu-Chun
Published: February 2024

Background

Haemaphysalis concinna, carrying multiple pathogens, has attracted increasing attention because of its expanded geographical range and significant role in disease transmission. This study aimed to identify the potential public health risks posed by H. concinna and H. concinna-associated pathogens.

Methods

A comprehensive database integrating a field survey, literature review, reference book, and relevant websites was developed. The geographical distribution of H. concinna and its associated pathogens was illustrated using ArcGIS. Meta-analysis was performed to estimate the prevalence of H. concinna-associated microbes. Phylogenetic and geographical methods were used to investigate the role of birds in the transmission of H. concinna-associated microbes. The potential global distribution of H. concinna was predicted by ecological niche modeling.

Results

Haemaphysalis concinna was distributed in 34 countries across the Eurasian continent, predominantly in China, Russia, and Central Europe. The tick species carried at least 40 human pathogens, including six species in the Anaplasmataceae family, five species of Babesia, four genospecies in the complex Borrelia burgdorferi sensu lato, ten species of spotted fever group rickettsiae, ten species of viruses, as well as Francisella, Coxiella, and other bacteria. Haemaphysalis concinna could parasitize 119 host species, with nearly half of them being birds, which played a crucial role in the long-distance transmission of tick-borne microbes. Our predictive modeling suggested that H. concinna could potentially survive in regions where the tick has never been previously recorded such as central North America, southern South America, southeast Oceania, and southern Africa.

Conclusions

Our study revealed the wide distribution, broad host range, and pathogen diversity of H. concinna. Authorities, healthcare professionals, and the entire community should address the growing threat of H. concinna and associated pathogens. Tick monitoring and control, pathogen identification, diagnostic tools, and continuous research should be enhanced.

Graphical Abstract
First-trimester HbA1c in relation to plasma glucose concentrations in an oral glucose tolerance test at 12 to 16 weeks’ gestation—a population-based study
Authors: Jokelainen Mervi , Kautiainen Hannu , Nenonen Arja , Stach-Lempinen Beata , Klemetti Miira M.
Published: February 2024

Background

Early-onset GDM often requires pharmacological treatment and is associated with adverse perinatal outcomes, but data is insufficient regarding the best methods to identify high-risk women requiring early GDM screening. The aim of this study was to analyze the diagnostic accuracy of HbA1c in the prediction of (1) plasma glucose concentrations > 90th percentile in an oral glucose tolerance test (OGTT) at 12–16 weeks’ gestation; and (2) pharmacologically treated early- or late-onset GDM.

Methods

HbA1c was measured at 8—14 weeks’ gestation in a population-based cohort of 1394 Finnish women recruited for the Early Diagnosis of Diabetes in Pregnancy (EDDIE) study between 3/2013 and 12/2016. Information on maternal risk factors were collected at recruitment. Subsequently, a 2-hour 75 g OGTT was performed at 12—16 weeks’ gestation (OGTT1), and if normal, repeated at 24–28 weeks’ gestation (OGTT2). Early- and late-onset GDM were diagnosed using the same nationally endorsed cut-offs for fasting, 1 h- and 2 h-plasma glucose: ≥5.3, ≥ 10.0mmol/l, and/or ≥ 8.6mmol/l, respectively. In total, 52/1394 (3.7%) women required metformin or insulin treatment for GDM, including 39 women with early-onset GDM diagnosed at OGTT1 and 13 women with late-onset GDM diagnosed at OGTT2.

Results

Maternal early-pregnancy HbA1c ≥ 35mmol/mol (≥ 5.4%) was the best cut-off to predict fasting or post-load plasma glucose > 90th percentile in OGTT1, but its diagnostic accuracy was low [AUC (95% CI) 0.65 (0.62 to 0.69), sensitivity 0.55 (0.49 to 0.60) and specificity 0.67 (0.64 to 0.70)] both alone and in combination with other maternal risk factors. However, HbA1c ≥ 35mmol/mol correlated positively with plasma glucose concentrations at all time points of OGTT1 and predicted pharmacologically treated GDM diagnosed at OGTT1 or OGTT2; AUC (95% CI) 0.75 (0.68 to 0.81), sensitivity 0.75 (0.61 to 0.86), specificity 0.64 (0.61 to 0.66).

Conclusions

In our population-based cohort, early-pregnancy HbA1c ≥ 35mmol/mol was positively associated with fasting and post-load plasma glucose concentrations in an OGTT at 12—16 weeks’ gestation and predicted pharmacologically-treated early- and late-onset GDM, suggesting potential utility in first-trimester identification of women at high risk of severe GDM subtypes.
Increased susceptibility to new-onset atrial fibrillation in diabetic women with poor sleep behaviour traits: findings from the prospective cohort study in the UK Biobank
Authors: Chen Siwei , Liu Zhou , Yan Shaohua , Du Zhongyan , Cheng Wenke
Published: February 2024

Background

Diabetic individuals often encounter various sleep-related challenges. Although the association between sleep duration and atrial fibrillation (AF) have been explored, the association of other sleep traits with the incidence of AF remains unclear. A comprehensive understanding of these traits is essential for a more accurate assessment of sleep conditions in patients with diabetes and the development of novel AF prevention strategies.

Methods

This study involved 23,785 patients with diabetes without any pre-existing cardiovascular disease, drawn from the UK Biobank. Sleep behaviour traits examined encompassed sleep duration, chronotype, insomnia, snoring and daytime sleepiness. Sleep duration was categorised into three groups: low (≤ 5 h), proper (6–8 h) and long (≥ 9 h). We assessed associations using multivariate Cox proportional risk regression models. Furthermore, four poor sleep behaviours were constructed to evaluate their impact on the risk of new-onset AF.

Results

Over a mean follow-up period of 166 months, 2221 (9.3%) new cases of AF were identified. Short (hazard ratio (HR), 1.28; 95% confidence interval (CI) 1.10–1.50) and long sleep durations (HR 1.16; 95% CI 1.03–1.32) consistently exhibited an elevated risk of AF compared to optimal sleep duration. Early chronotype, infrequent insomnia and daytime sleepiness were associated with 11% (HR 0.89; 95% CI 0.82–0.97), 15% (HR 0.85; 95% CI 0.77–0.95) and 12% (HR 0.88; 95% CI 0.81–0.96) reduced risk of new-onset AF, respectively. However, no significant association was found between snoring and the incidence of AF (HR 0.99; 95% CI 0.91–1.07).

Conclusions

In diabetic populations, sleep duration, chronotype, insomnia and daytime sleepiness are strongly associated with AF incidence. An optimal sleep duration of 6–8 h presents the lowest AF risk compared to short or long sleep duration. Additionally, poor sleep patterns present a greater risk of new-onset AF in women than in men.
Identification of enterotype and its predictive value for patients with colorectal cancer
Authors: Qingbo Li , Jing Zhuang , Zhanbo Qu , Jian Chu , Yifei Song , Yinhang Wu , Shuwen Han
Published: February 2024

Background

Gut microbiota dysbiosis involved in the pathogenesis of colorectal cancer (CRC). The characteristics of enterotypes in CRC development have not been determined.

Objective

To characterize the gut microbiota of healthy, adenoma, and CRC subjects based on enterotype.

Methods

The 16 S rRNA sequencing data from 315 newly sequenced individuals and three previously published datasets were collected, providing total data for 367 healthy, 320 adenomas, and 415 CRC subjects. Enterotypes were analyzed for all samples, and differences in microbiota composition across subjects with different disease states in each enterotype were determined. The predictive values of a random forest classifier based on enterotype in distinguishing healthy, adenoma, and CRC subjects were evaluated and validated.

Results

Subjects were classified into one of three enterotypes, namely, Bacteroide- (BA_E), Blautia- (BL_E), and Streptococcus- (S_E) dominated clusters. The taxonomic profiles of these three enterotypes differed among the healthy, adenoma, and CRC cohorts. BA_E group was enriched with Bacteroides and Blautia; BL_E group was enriched by Blautia and Coprococcus; S_E was enriched by Streptococcus and Ruminococcus. Relative abundances of these genera varying among the three human cohorts. In training and validation sets, the S_E cluster showed better performance in distinguishing among CRC patients, adenoma patients, and healthy controls, as well as between CRC and non-CRC individuals, than the other two clusters.

Conclusion

This study provides the first evidence to indicate that changes in the microbial composition of enterotypes are associated with disease status, thereby highlighting the diagnostic potential of enterotypes in the treatment of adenoma and CRC.
CT and MRI radiomics of bone and soft-tissue sarcomas: an updated systematic review of reproducibility and validation strategies
Authors: Gitto Salvatore , Cuocolo Renato , Huisman Merel , Messina Carmelo , Albano Domenico , Omoumi Patrick , Kotter Elmar , Maas Mario , Van Ooijen Peter , Sconfienza Luca Maria
Published: February 2024

Objective

To systematically review radiomic feature reproducibility and model validation strategies in recent studies dealing with CT and MRI radiomics of bone and soft-tissue sarcomas, thus updating a previous version of this review which included studies published up to 2020.

Methods

A literature search was conducted on EMBASE and PubMed databases for papers published between January 2021 and March 2023. Data regarding radiomic feature reproducibility and model validation strategies were extracted and analyzed.

Results

Out of 201 identified papers, 55 were included. They dealt with radiomics of bone (n = 23) or soft-tissue (n = 32) tumors. Thirty-two (out of 54 employing manual or semiautomatic segmentation, 59%) studies included a feature reproducibility analysis. Reproducibility was assessed based on intra/interobserver segmentation variability in 30 (55%) and geometrical transformations of the region of interest in 2 (4%) studies. At least one machine learning validation technique was used for model development in 34 (62%) papers, and K-fold cross-validation was employed most frequently. A clinical validation of the model was reported in 38 (69%) papers. It was performed using a separate dataset from the primary institution (internal test) in 22 (40%), an independent dataset from another institution (external test) in 14 (25%) and both in 2 (4%) studies.

Conclusions

Compared to papers published up to 2020, a clear improvement was noted with almost double publications reporting methodological aspects related to reproducibility and validation. Larger multicenter investigations including external clinical validation and the publication of databases in open-access repositories could further improve methodology and bring radiomics from a research area to the clinical stage.

Critical relevance statement

An improvement in feature reproducibility and model validation strategies has been shown in this updated systematic review on radiomics of bone and soft-tissue sarcomas, highlighting efforts to enhance methodology and bring radiomics from a research area to the clinical stage.

Key points

• 2021–2023 radiomic studies on CT and MRI of musculoskeletal sarcomas were reviewed.

• Feature reproducibility was assessed in more than half (59%) of the studies.

• Model clinical validation was performed in 69% of the studies.

• Internal (44%) and/or external (29%) test datasets were employed for clinical validation.

Graphical Abstract
Prognostic value of right atrial strains in arrhythmogenic right ventricular cardiomyopathy
Authors: Zheng Jin-Yu , Chen Bing-Hua , Wu Rui , An Dong-Aolei , Shi Ruo-Yang , Wu Chong-Wen , Tang Lang-Lang , Zhao Lei , Wu Lian-Ming
Published: February 2024

Objectives

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty infiltration of atrial and ventricular myocardium resulting in adverse cardiac events. Atrial function has been increasingly recognized as prognostically important for cardiovascular disease. As the right atrial (RA) strain is a sensitive parameter to describe RA function, we aimed to analyze the prognostic value of the RA strain in ARVC.

Methods

RA strain parameters were derived from cardiac magnetic resonance (CMR) images of 105 participants with definite ARVC. The endpoint was defined as a combination of sudden cardiac death, survival cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. Cox regression and Kaplan–Meier survival analyses were performed to evaluate the association between RA strain parameters and endpoint. Concordance index (C index), net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the incremental value of RA strain in predicting the endpoint.

Results

After a median follow-up of 5 years, 36 (34.3%) reaching the endpoint displayed significantly reduced RA strain parameters. At Kaplan–Meier analysis, impaired RA reservoir (RARS) and booster strains (RABS) were associated with an increased risk of the endpoint. After adjusting for conventional risk factors, RARS (hazard ratio [HR], 0.956; p = 0.005) and RABS (HR, 0.906; p = 0.002) resulted as independent predictors for endpoint at Cox regression analyses. In addition, RARS and RABS improved prognostic value to clinical risk factors and CMR morphological and functional predictors (all p < 0.05).

Conclusion

RARS and RABS were independent predictors for adverse cardiac events, which could provide incremental prognostic value for conventional predictors in ARVC.

Critical relevance statement

We evaluated the prognostic value of right atrial strain in ARVC patients and suggested cardiologists consider RA strain as a predictive parameter when evaluating the long-term outcome of ARVC patients in order to formulate better clinical therapy.

Key points

• Patients with ARVC had significantly reduced RA strain and strain rates compared with healthy participants.

• Participants with lower RA reservoir and booster stains were associated with a significantly higher risk of adverse cardiac events.

• RA booster and reservoir strain provide incremental value to conventional parameters.

Graphical Abstract
Equine enteroid-derived monolayers recapitulate key features of parasitic intestinal nematode infection
Authors: Hellman Stina , Martin Frida , Tydén Eva , Sellin Mikael E. , Norman Albin , Hjertner Bernt , Svedberg Pia , Fossum Caroline
Published: February 2024

Stem cell-derived organoid cultures have emerged as attractive experimental models for infection biology research regarding various types of gastro-intestinal pathogens and host species. However, the large size of infectious nematode larvae and the closed structure of 3-dimensional organoids often hinder studies of the natural route of infection. To enable easy administration to the apical surface of the epithelium, organoids from the equine small intestine, i.e. enteroids, were used in the present study to establish epithelial monolayer cultures. These monolayers were functionally tested by stimulation with IL-4 and IL-13, and/or exposure to infectious stage larvae of the equine nematodes Parascaris univalens, cyathostominae and/or Strongylus vulgaris. Effects were recorded using transcriptional analysis combined with histochemistry, immunofluorescence-, live-cell- and scanning electron microscopy. These analyses revealed heterogeneous monolayers containing both immature and differentiated cells including tuft cells and mucus-producing goblet cells. Stimulation with IL-4/IL-13 increased tuft- and goblet cell differentiation as demonstrated by the expression of DCLK1 and MUC2. In these cytokine-primed monolayers, the expression of MUC2 was further promoted by co-culture with P. univalens. Moreover, live-cell imaging revealed morphological alterations of the epithelial cells following exposure to larvae even in the absence of cytokine stimulation. Thus, the present work describes the design, characterization and usability of an experimental model representing the equine nematode-infected small intestinal epithelium. The presence of tuft cells and goblet cells whose mucus production is affected by Th2 cytokines and/or the presence of larvae opens up for mechanistic studies of the physical interactions between nematodes and the equine intestinal mucosa.
Molecular mechanism of bovine Gasdermin D-mediated pyroptosis
Authors: Ge Zhendong , Xu Jinxia , Yang Ke , Wu Longjian , Chen Shan , Chen Biao , Tian Jiangyao , Zhang Jinpeng , Xu Ahui , Huang Bei , Song Houhui , Yang Yang
Published: February 2024

Pyroptosis is a form of programmed cell death characterized by cell swelling, pore formation in the plasma membrane, lysis, and releases of cytoplasmic contents. To date, the molecular mechanism of human and murine Gasdermin D-mediated pyroptosis have been fully investigated. However, studies focusing on molecular mechanism of bovine Gasdermin D (bGSDMD)-mediated pyroptosis and its function against pathogenic infection were unclear. In the present study, we demonstrate that bovine caspase-1 (bCaspase-1) cleaves bGSDMD at amino acid residue D277 to produce an N-terminal fragment (bGSDMD-p30) which leads to pyroptosis. The amino acid residues T238 and F239 are critical for bGSDMD-p30-mediated pyroptosis. The loop aa 278-299, L293 and A380 are the key sites for autoinhibitory structure of the full length of bGSDMD. In addition, bCaspase-3 also cleaves bGSDMD at residue Asp86 without inducing cell death. Therefore, our study provides the first detailed elucidation of the mechanism of bovine GSDMD-mediated pyroptosis. The results will establish a significant foundation for future research on the role of pyroptosis in bovine infectious diseases.
Immediate vs. culture-initiated antibiotic therapy in suspected non-severe ventilator-associated pneumonia: a before–after study (DELAVAP)
Authors: Martin Maëlle , Forveille Solène , Lascarrou Jean-Baptiste , Seguin Amélie , Canet Emmanuel , Lemarié Jérémie , Agbakou Maïté , Desmedt Luc , Blonz Gauthier , Zambon Olivier , Corvec Stéphane , Le Thuaut Aurélie , Reignier Jean
Published: February 2024

Background

Ventilator-associated pneumonia (VAP) is the leading nosocomial infection in critical care and is associated with adverse outcomes. When VAP is suspected, starting antibiotic therapy (AT) immediately after pulmonary sampling may expose uninfected patients to unnecessary treatment, whereas waiting for bacteriological confirmation may delay AT in infected patients. As no robust data exist to choose between these strategies, the decision must balance the pre-test diagnostic probability, clinical severity, and risk of antimicrobial resistance. The objective of this study in patients with suspected non-severe VAP was to compare immediate AT started after sampling to conservative AT upon receipt of positive microbiological results. The outcomes were antibiotic sparing, AT suitability, and patient outcomes.

Methods

This single-center, before–after study included consecutive patients who underwent distal respiratory sampling for a first suspected non-severe VAP episode (no shock requiring vasopressor therapy or severe acute respiratory distress syndrome). AT was started immediately after sampling in 2019 and upon culture positivity in 2022 (conservative strategy). The primary outcome was the number of days alive without AT by day 28. The secondary outcomes were mechanical ventilation duration, day-28 mortality, and AT suitability (active necessary AT or spared AT).

Results

The immediate and conservative strategies were applied in 44 and 43 patients, respectively. Conservative and immediate AT were associated with similar days alive without AT (median [interquartile range], 18.0 [0–21.0] vs. 16.0 [0–20.0], p = 0.50) and without broad-spectrum AT (p = 0.53) by day 28. AT was more often suitable in the conservative group (88.4% vs. 63.6%, p = 0.01), in which 27.9% of patients received no AT at all. No significant differences were found for mechanical ventilation duration (median [95%CI], 9.0 [6–19] vs. 9.0 [6–24] days, p = 0.65) or day-28 mortality (hazard ratio [95%CI], 0.85 [0.4–2.0], p = 0.71).

Conclusion

In patients with suspected non-severe VAP, waiting for microbiological confirmation was not associated with antibiotic sparing, compared to immediate AT. This result may be ascribable to low statistical power. AT suitability was better with the conservative strategy. None of the safety outcomes differed between groups. These findings would seem to allow a large, randomized trial comparing immediate and conservative AT strategies.
Azerbaijani adaptation of the WHO-5 wellbeing index: investigating its relationship with psychological distress, resilience, and life satisfaction
Authors: Aliyev Bakhtiyar , Rustamov Elnur , Satici Seydi Ahmet , Zalova Nuriyeva Ulkar
Published: February 2024

Background

The WHO-5 Wellbeing Index is a widely used tool for assessing psychological well-being. Despite its global application, its adaptation and validation for the Azerbaijani population had not been previously explored. This study aims to fill this gap by adapting the WHO-5 Wellbeing Index for Azerbaijani adults and examining its relationship with psychological distress, resilience, and life satisfaction.

Methods

A sample of 875 Azerbaijani adults aged 18 to 89 (mean age = 29.13, SD = 10.98) participated in this study. The adaptation process included confirmatory factor analysis to test the original 5-item structure of the index in the Azerbaijani context. Additionally, item response theory analysis was employed to evaluate the discriminative values of the items. Reliability was assessed through various methods, including Cronbach’s alpha, McDonald’s omega, and Guttmann’s lambda.

Results

Confirmatory factor analysis supported the original 5-item structure of the WHO-5 Wellbeing Index for the Azerbaijani sample, demonstrating alignment with the index’s original version. All items showed acceptable discriminative values in item response theory analysis. The index also exhibited sufficient reliability, as evidenced by Cronbach’s alpha, McDonald’s omega, and Guttmann’s lambda. Correlation and network analyses indicated significant associations of the WHO-5 Wellbeing Index with psychological distress, resilience, and life satisfaction. Specifically, the index was negatively correlated with depression, anxiety, and stress, and positively correlated with resilience and life satisfaction.

Conclusion

The findings suggest that the WHO-5 Wellbeing Index is a valid and reliable tool for assessing psychological well-being in the Azerbaijani population. Its significant associations with psychological distress, resilience, and life satisfaction further affirm its utility in this cultural context.
Capecitabine-induced-coronary-vasospasm leading to polymorphic ventricular tachycardia and cardiac arrest
Authors: Kabat Maciej , Padalkar Roma , Hazaveh Sara , Joseph Vladimir , Feigenblum David , Sadikot Sean
Published: February 2024

Capecitabine, a pro-drug of 5-fluorouracil, is commonly used in the treatment of breast and colorectal cancer. Its side effects, including nausea, vomiting, diarrhea, fatigue, loss of appetite, and bone marrow suppression, are well recognized. However, coronary vasospasm represents a less commonly recognized but significant complication of fluoropyrimidine-based therapies such as capecitabine. Proposed mechanisms for this adverse effect complication include direct endothelium-independent vasoconstriction, activation of protein kinase C, and activation of the cyclooxygenase pathway. In this report, we present a case of capecitabine-induced coronary vasospasm leading to progressive, focal ST-elevations, myocardial ischemia, and subsequently polymorphic ventricular tachycardia. These events were captured on telemetry, in a male in his early 40s, diagnosed with stage IIIB sigmoid colon cancer. Notably, the patient had no pre-existing coronary artery disease or other cardiovascular risk factors. Upon diagnosis, the patient was initiated on a calcium channel blocker, verapamil, to mitigate further coronary vasospasm events. After thorough discussions that prioritized the patient’s input and values, an implantable cardioverter-defibrillator was placed subcutaneously. Following discharge, the patient restarted capecitabine therapy along with verapamil prophylaxis and did not experience any subsequent shocks from his ICD as assessed during his outpatient follow-up visits. This case emphasizes the need to involve patients in decision-making processes, especially when managing unexpected and serious complications, to ensure treatments align with their quality of life and personal preferences.