bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging-based body fat depots and new-onset atrial fibrillation in general population: a prospective cohort study
Authors: Lu Zuolin , Tilly Martijn J. , Aribas Elif , Bos Daniel , Geurts Sven , Stricker Bruno H. , de Knegt Robert , Ikram M. Arfan , de Groot Natasja M. S. , Voortman Trudy , Kavousi Maryam 
Published: September 2022

Abstract
Background
Obesity is a well-established risk factor for atrial fibrillation (AF). Whether body fat depots differentially associate with AF development remains unknown.

Methods
In the prospective population-based Rotterdam Study, body composition was assessed using dual-energy X-ray absorptiometry (DXA) and liver and epicardial fat using computed tomography (CT). A body composition score was constructed by adding tertile scores of each fat depot. Principal component analysis was conducted to identify potential body fat distribution patterns. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals (HR; 95% CI) per 1-standard deviation increase in corresponding fat depots to enable comparisons.

Results
Over a median follow-up of 9.6 and 8.6 years, 395 (11.4%) and 172 (8.0%) AF cases were ascertained in the DXA and the CT analyses, respectively. After adjustments for cardiovascular risk factors, absolute fat mass (HR; 95% CI 1.33; 1.05–1.68), gynoid fat mass (HR; 95% CI 1.36; 1.12–1.65), epicardial fat mass (HR; 95% CI 1.27; 1.09-1.48), and android-to-gynoid fat ratio (HR; 95% CI 0.81; 0.70-0.94) were independently associated with new-onset AF. After further adjustment for lean mass, associations between fat mass (HR; 95% CI 1.17; 1.04-1.32), gynoid fat mass (HR; 95% CI 1.21; 1.08–1.37), and android-to-gynoid fat ratio (HR; 95% CI 0.84; 0.72–0.97) remained statistically significant. Larger body fat score was associated with a higher AF risk (HR; 95% CI 1.10; 1.02–1.20). Borderline significant association was found between a subcutaneous fat predominant pattern with AF onset (HR; 95% CI 1.21; 0.98–1.49).

Conclusions
Various body fat depots were associated with new-onset AF. Total fat mass and gynoid fat mass were independently associated with AF after adjustment for body size. The inverse association between android-to-gynoid fat ratio with AF presents a novel finding. A significant dose-response relationship between body fat accumulation and AF was observed. Our results underscore the predominant role of subcutaneous fat on AF development among a middle-aged and elderly population.

Graphical abstract
Associations betw2een body fat depots, fat distribution and new-onset atrial fibrillation. Abbreviations: AF, atrial fibrillation.
Challenges in the diagnosis of asthma in children, what are the solutions? A scoping review of 3 countries in sub Saharan Africa
Authors: Magwenzi P. , Rusakaniko S. , Sibanda E. N. , Gumbo F. Z. 
Published: September 2022

AbstractBackgroundAsthma is the commonest chronic respiratory tract disease in children. In low-income countries, challenges exist in asthma diagnosis. In surveys done in children, the prevalence of ‘asthma’ defined by symptoms is high compared to ‘doctor diagnosed asthma’. The questions answered by this review are (i) What challenges have been experienced in the diagnosis of asthma in children? (ii) What solutions will address these challenges?MethodsThe Arksey and O’Malley’s framework for scoping reviews was used for the study methodology, while the PRISMA-ScR checklist guided the reporting process. Electronic databases: PubMed Central, EMBASE and Google Scholar were searched. Primary quantitative and qualitative studies and reviews from 2010 to 2021, from Nigeria, South Africa and Uganda written in English or translated to English, which answered the study questions were included. The author, title, country, study type, methods, purpose, findings and references were captured onto a predefined data collection table. The ‘Preview, Question, Read, Summarise’ system was used and a narrative report was used to summarise the findings.ResultsA total of 28 studies were included. The causes of under-diagnosis of asthma include lack of community knowledge and perception of asthma, poor accessibility to health care, strained health systems, lack of diagnostic tests including spirometry, low levels of knowledge among health-care workers and lack of or non-implementation of asthma guidelines. Strategies to improve asthma diagnosis will include community and school based education programmes, revision of asthma diagnostic terms, guideline development and implementation and health systems strengthening.ConclusionThis scoping review provides research evidence for policy makers and health-workers involved in the care of asthmatic children on challenges faced in asthma diagnosis and strategies to improve asthma diagnosis.
Safety during interhospital helicopter transfer of ventilated COVID-19 patients. No clinical relevant changes in vital signs including non-invasive cardiac output
Authors: Slagt Cornelis , Spoelder Eduard Johannes , Tacken Marijn Cornelia Theresia , Frijlink Maartje , Servaas Sjoerd , Leijte Guus , van Eijk Lucas Theodorus , van Geffen Geert Jan 
Published: September 2022

Abstract
Background
During the COVID-19 pandemic in The Netherlands, critically ill ventilated COVID-19 patients were transferred not only between hospitals by ambulance but also by the Helicopter Emergency Medical Service (HEMS). To date, little is known about the physiological impact of helicopter transport on critically ill patients and COVID-19 patients in particular. This study was conducted to explore the impact of inter-hospital helicopter transfer on vital signs of mechanically ventilated patients with severe COVID-19, with special focus on take-off, midflight, and landing.

Methods
All ventilated critically ill COVID-19 patients who were transported between April 2020 and June 2021 by the Dutch ‘Lifeliner 5’ HEMS team and who were fully monitored, including noninvasive cardiac output, were included in this study. Three 10-min timeframes (take-off, midflight and landing) were defined for analysis. Continuous data on the vital parameters heart rate, peripheral oxygen saturation, arterial blood pressure, end-tidal CO2 and noninvasive cardiac output using electrical cardiometry were collected and stored at 1-min intervals. Data were analyzed for differences over time within the timeframes using one-way analysis of variance. Significant differences were checked for clinical relevance.

Results
Ninety-eight patients were included in the analysis. During take-off, an increase was noticed in cardiac output (from 6.7 to 8.2 L min−1; P < 0.0001), which was determined by a decrease in systemic vascular resistance (from 1071 to 739 dyne·s·cm−5, P < 0.0001) accompanied by an increase in stroke volume (from 88.8 to 113.7 mL, P < 0.0001). Other parameters were unchanged during take-off and mid-flight. During landing, cardiac output and stroke volume slightly decreased (from 8.0 to 6.8 L min−1, P < 0.0001 and from 110.1 to 84.4 mL, P < 0.0001, respectively), and total systemic vascular resistance increased (P < 0.0001). Though statistically significant, the found changes were small and not clinically relevant to the medical status of the patients as judged by the attending physicians.

Conclusions
Interhospital helicopter transfer of ventilated intensive care patients with COVID-19 can be performed safely and does not result in clinically relevant changes in vital signs.
Integrated multi-omics analysis and microbial recombinant protein system reveal hydroxylation and glycosylation involving nevadensin biosynthesis in Lysionotus pauciflorus
Authors: Wu Tianze , Xiang Li , Gao Ranran , Wu Lan , Deng Gang , Wang Wenting , Zhang Yongping , Wang Bo , Shen Liang , Chen Shilin , Liu Xia , Yin Qinggang 
Published: September 2022

AbstractBackgroundKarst-adapted plant,Lysionotus paucifloursaccumulates special secondary metabolites with a wide range of pharmacological effects for surviving in drought and high salty areas, while researchers focused more on their environmental adaptations and evolutions. Nevadensin (5,7-dihydroxy-6,8,4'-trimethoxyflavone), the main active component inL. pauciflours,has unique bioactivity of such as anti-inflammatory, anti-tubercular, and anti-tumor or cancer. Complex decoration of nevadensin, such as hydroxylation and glycosylation of the flavone skeleton determines its diversity and biological activities. The lack of omics data limits the exploration of accumulation mode and biosynthetic pathway. Herein, we integrated transcriptomics, metabolomics, and microbial recombinant protein system to reveal hydroxylation and glycosylation involving nevadensin biosynthesis inL. pauciflours.ResultsUp to 275 flavonoids were found to exist inL. pauciflorusby UPLC-MS/MS based on widely targeted metabolome analysis. The special flavone nevadensin (5,7-dihydroxy-6,8,4'-trimethoxyflavone) is enriched in different tissues, as are its related glycosides. The flavonoid biosynthesis pathway was drawn based on differential transcripts analysis, including 9 PAL, 5 C4H, 8 4CL, 6 CHS, 3 CHI, 1 FNSII, and over 20 OMTs.Total 310 LpCYP450s were classified into 9 clans, 36 families, and 35 subfamilies, with 56% being A-type CYP450s by phylogenetic evolutionary analysis. According to the phylogenetic tree with AtUGTs, 187 LpUGTs clustered into 14 evolutionary groups (A-N), with 74% being E, A, D, G, and K groups.Two LpCYP82D members and LpUGT95 were functionally identified inSaccharomyces cerevisiaeandEscherichia coli, respectively.CYP82D-8 and CYP82D-1 specially hydroxylate the 6- or 8-position of A ring in vivo and in vitro, dislike the function of F6H or F8H discovered in basil which functioned depending on A-ring substituted methoxy. These results refreshed the starting mode that apigenin can be firstly hydroxylated on A ring in nevadensin biosynthesis. Furthermore, LpUGT95 clustered into the 7-OGT family was verified to catalyze 7-O glucosylation of nevadensin accompanied with weak nevadensin 5-O glucosylation function, firstly revealed glycosylation modification of flavones with completely substituted A-ring.ConclusionsMetabolomic and full-length transcriptomic association analysis unveiled the accumulation mode and biosynthetic pathway of the secondary metabolites in the karst-adapted plantL. pauciflorus. Moreover, functional identification of two LpCYP82D members and one LpUGT in microbe reconstructed the pathway of nevadensin biosynthesis.
YY1 promotes pancreatic cancer cell proliferation by enhancing mitochondrial respiration
Authors: Li Bin , Wang Junyi , Liao Jing , Wu Minghui , Yuan Xiangshu , Fang Hezhi , Shen Lijun , Jiang Minghua 
Published: September 2022

AbstractKRAS-driven metabolic reprogramming is a known peculiarity features of pancreatic ductal adenocarcinoma (PDAC) cells. However, the metabolic roles of other oncogenic genes, such as YY1, in PDAC development are still unclear. In this study, we observed significantly elevated expression of YY1 in human PDAC tissues, which positively correlated with a poor disease progression. Furthermore, in vitro studies confirmed that YY1 deletion inhibited PDAC cell proliferation and tumorigenicity. Moreover, YY1 deletion led to impaired mitochondrial RNA expression, which further inhibited mitochondrial oxidative phosphorylation (OXPHOS) complex assembly and altered cellular nucleotide homeostasis. Mechanistically, the impairment of mitochondrial OXPHOS function reduced the generation of aspartate, an output of the tricarboxylic acid cycle (TCA), and resulted in the inhibition of cell proliferation owing to unavailability of aspartate-associated nucleotides. Conversely, exogenous supplementation with aspartate fully restored PDAC cell proliferation. Our findings suggest that YY1 promotes PDAC cell proliferation by enhancing mitochondrial respiration and the TCA, which favors aspartate-associated nucleotide synthesis. Thus, targeting nucleotide biosynthesis is a promising strategy for PDAC treatment.
Cultural and ethnobotanical legacy of native potatoes in Colombia
Authors: Galvis-Tarazona Daicy Yaneth , Ojeda-Pérez Zaida Zarely , Arias-Moreno Diana Marcela 
Published: September 2022

Abstract
Background
Native potatoes are Andean tubers of great historical, social, food, genetic and nutritional importance, and they contribute significantly to food security by supplementing the household diet and also providing alternative income. Even when their cultivation and consumption imply great benefits, their use and local preservation depend to a large extent on the recognition of their ethnobotanical and cultural importance. In this context, this study consolidates an important ethnobotanical research bases for native potatoes in Colombia.

Methods
The study collected data through semi-structured interviews and dialogues (130) in the municipality of Chiscas, department of Boyacá, central-eastern Colombia. The questionnaire was focused on native potatoes and sought to investigate the knowledge related to cultivation, diversity, patterns and forms of preparation for use and consumption. Likewise, knowledge heritability mechanisms were investigated and ethnobotanical indices of relative importance, use and culture were estimated.

Results
Documentation of ethnobotanical knowledge included aspects such as seed care and availability, cultural management of the crop, patterns of use and consumption, as well as ways of preparing the tubers. In total, 23 vernacular names of native potato and 360 reports of use (commercial, domestic or ritual-magical) were recorded for the 15 main genotypes. Quantitative estimates included the importance index: (a) cultural, for which values ranged between 0.059 and 0.812; (b) relative, with records between 0.04 and 0.43; and (c) use, which ranged between 0.06 and 0.63. The ethnobotanical importance index (d) for native potatoes was 57.26, which corresponds to a “very high” ethnobotanical value. This allowed us to identify that Criollas were the most recognized and used potatoes within the community. In addition, it was shown that vertical transmission is the main way in which traditional knowledge about native potatoes is inherited. Finally, an artificial intelligence tool was preliminarily implemented to identify the polarity generated in the interviewees by the questions.

Conclusion
The results of this research provide valuable information on the ethnobotany of native potatoes in Colombia. The genotypes used by the community of the municipality of Chiscas were recognized for their high gastronomic and nutritional potential, as well as for their great ethnobotanical and cultural importance. These data can be considered as a valuable tool to support any action aimed at the conservation and revaluation of these tubers.
Tourniquet use following blast-associated complex lower limb injury and traumatic amputation promotes end organ dysfunction and amplified heterotopic ossification formation
Authors: Spreadborough Philip J. , Strong Amy L. , Mares John , Levi Benjamin , Davis Thomas A. 
Published: September 2022

AbstractBackgroundTraumatic heterotopic ossification (tHO) is characterized by ectopic bone formation in extra-skeletal sites leading to impaired wound healing, entrapment of neurovascular structures, pain, and reduced range of motion. HO has become a signature pathology affecting wounded military personnel who have sustained blast-associated traumatic amputations during the recent conflicts in Iraq and Afghanistan and can compound recovery by causing difficulty with prosthesis limb wearing. Tourniquet use to control catastrophic limb hemorrhage prior to surgery has become almost ubiquitous during this time, with the recognition the prolonged use may risk an ischemia reperfusion injury and associated complications. While many factors influence the formation of tHO, the extended use of tourniquets to limit catastrophic hemorrhage during prolonged field care has not been explored.MethodsUtilizing an established pre-clinical model of blast-associated complex lower limb injury and traumatic amputation, we evaluated the effects of tourniquet use on tHO formation. Adult male rats were subjected to blast overpressure exposure, femur fracture, and soft tissue crush injury. Pneumatic tourniquet (250–300 mmHg) applied proximal to the injured limb for 150-min was compared to a control group without tourniquet, before a trans-femoral amputation was performed. Outcome measures were volume to tHO formation at 12 weeks and changes in proteomic and genomic markers of early tHO formation between groups.ResultsAt 12 weeks, volumetric analysis with microCT imaging revealed a 70% increase in total bone formation (p = 0.007) near the site of injury compared to rats with no tourniquet time in the setting of blast-injuries. Rats subjected to tourniquet usage had increased expression of danger-associated molecular patterns (DAMPs) and end organ damage as early as 6 h and as late as 7 days post injury. The expressions of pro-inflammatory cytokines and chemokines and osteochondrogenic genes using quantitative RT-PCR similarly revealed increased expression as early as 6 h post injury, and these genes along with hypoxia associated genes remained elevated for 7 days compared to no tourniquet use.ConclusionThese findings suggest that tourniquet induced ischemia leads to significant increases in key transcription factors associated with early endochondral bone formation, systemic inflammatory and hypoxia, resulting in increased HO formation.
Surgical correction of total anomalous pulmonary venous return in an adult patient
Authors: Bae Yohan , Jang Woo Sung , Song Kyungsub 
Published: September 2022

Abstract
Background
Total anomalous pulmonary venous return (TAPVR) is rare congenital heart disease. Most TAPVRs require surgical corrections in the neonatal period and survival to adulthood without surgical correction is extremely rare. Most untreated patients with large atrial septal defects and no pulmonary venous obstruction have pulmonary vascular damage from pulmonary over circulation.

Case presentation
44-year-old TAPVR patient admitted to our medical center. A snowman-shaped heart, including cardiomegaly and an increase in pulmonary blood flow, was seen in the chest X-ray. A large-sized (around 3 cm) atrial septal defect with dilated right atrium, right ventricle, and pulmonary artery was detected on echocardiography. Heart computed tomography was performed for further evaluation, and supra-cardiac type TAPVR without any obstructive lesion was identified.

Conclusions
TAPVR in an adult patient is extremely rare, and this patient was treated successfully with surgical correction and is doing well. A sinus rhythm and mild mitral valve regurgitation have remained during 2.5 years of outpatient follow-up.
Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center
Authors: Monet Clément , De Jong Audrey , Aarab Yassir , Piron Lauranne , Prades Albert , Carr Julie , Belafia Fouad , Chanques Gérald , Guiu Boris , Pageaux Georges-Philippe , Jaber Samir 
Published: September 2022

AbstractBackgroundMolecular Adsorbent Recirculating System (MARS®) is a non-biological artificial liver device. The benefit risk ratio between uncertain clinical effects and potential adverse events remains difficult to assess. We sought to describe adverse events related to MARS® therapy as well as biological and clinical effects.MethodsAll intensive care unit (ICU) admissions to whom MARS® therapy was prescribed from March 2005 to August 2021 were consecutively and prospectively included. The main endpoint was the incidence of adverse events related to MARS® therapy. Secondary endpoints were the biological and clinical effects of MARS® therapy.ResultsWe reported 180 admissions treated with MARS® therapy. Among the 180 admissions, 56 (31.1%) were for acute-on-chronic liver failure, 32 (17.8%) for acute liver failure, 28 (15.5%) for post-surgery liver failure, 52 (28.9%) for pruritus and 12 (6.7%) for drug intoxication. At least one adverse event occurred in 95 (52.8%) admissions. Thrombocytopenia was the most frequent adverse event which was recorded in 55 admissions (30.6%). Overall, platelets count was 131 (± 95) × 109/L before and 106 (± 72) × 109/L after MARS® therapy (p < .001). After MARS® therapy, total bilirubin was significantly decreased in all groups (p < 0.05). Hepatic encephalopathy significantly improved in both the acute-on-chronic and in the acute liver failure group (p = 0.01). In the pruritus group, pruritus intensity score was significantly decreased after MARS® therapy (p < 0.01).ConclusionIn this large cohort of patients treated with MARS® therapy we report frequent adverse events. Thrombocytopenia was the most frequent adverse event. In all applications significant clinical and biological improvements were shown with MARS® therapy.
Impact of tight blood glucose control within normal fasting ranges with insulin titration prescribed by the Leuven algorithm in adult critically ill patients: the TGC-fast randomized controlled trial
Authors: Gunst Jan , Mebis Liese , Wouters Pieter J. , Hermans Greet , Dubois Jasperina , Wilmer Alexander , Hoste Eric , Benoit Dominique , Van den Berghe Greet 
Published: September 2022

Abstract
Background
It remains controversial whether critical illness-related hyperglycemia should be treated or not, since randomized controlled trials (RCTs) have shown context-dependent outcome effects. Whereas pioneer RCTs found improved outcome by normalizing blood glucose in patients receiving early parenteral nutrition (PN), a multicenter RCT revealed increased mortality in patients not receiving early PN. Although withholding early PN has become the feeding standard, the multicenter RCT showing harm by tight glucose control in this context has been criticized for its potentially unreliable glucose control protocol. We hypothesize that tight glucose control is effective and safe using a validated protocol in adult critically ill patients not receiving early PN.

Methods
The TGC-fast study is an investigator-initiated, multicenter RCT. Patients unable to eat, with need for arterial and central venous line and without therapy restriction, are randomized upon ICU admission to tight (80–110 mg/dl) or liberal glucose control (only initiating insulin when hyperglycemia >215 mg/dl, and then targeting 180–215 mg/dl). Glucose measurements are performed on arterial blood by a blood gas analyzer, and if needed, insulin is only administered continuously through a central venous line. If the arterial line is no longer needed, glucose is measured on capillary blood. In the intervention group, tight control is guided by the validated LOGIC-Insulin software. In the control arm, a software alert is used to maximize protocol compliance. The intervention is continued until ICU discharge, until the patient is able to eat or no longer in need of a central venous line, whatever comes first. The study is powered to detect, with at least 80% power and a 5% alpha error rate, a 1-day difference in ICU dependency (primary endpoint), and a 1.5% increase in hospital mortality (safety endpoint), for which 9230 patients need to be included. Secondary endpoints include acute and long-term morbidity and mortality, and healthcare costs. Biological samples are collected to study potential mechanisms of organ protection.

Discussion
The ideal glucose target for critically ill patients remains debated. The trial will inform physicians on the optimal glucose control strategy in adult critically ill patients not receiving early PN.

Trial registration
ClinicalTrials.gov NCT03665207. Registered on 11 September 2018.