bluuebunny/crossref_metadata_2025_split 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

Abstract
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

Abstract
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

Abstract
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

AbstractGastrointestinal 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

AbstractWith 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

AbstractBackgroundMitochondrial 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.MethodsMolecular 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.ResultsHes 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.ConclusionHes 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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