bluuebunny/crossref_metadata_2025_split huggingface dataset:
Documentary analysis of national and international guidance for community clinicians referring patients with suspected chronic limb-threatening ischaemia
Authors: Atkins Eleanor , Birmpili Panagiota , Kellar Ian , Glidewell Liz , Cromwell David A 
Published: May 2024

BackgroundDelayed referral of patients with chronic limb-threatening ischaemia (CLTI) from the community to vascular services may increase risk of amputation due to delayed revascularisation. Lack of appropriate guidance for clinicians in the community may contribute to this problem. This documentary analysis investigated referral guidance available to primary care clinicians.MethodsNational and international documents providing guidance on CLTI management were identified by searching sources including Medline, Embase, Guidelines International Network and College/Society websites. Data were extracted on referral recommendations, target audience and author groups. Recommendations were coded according to the Behaviour Change Technique Taxonomy. Clinical practice guideline quality and ease of implementation were assessed independently by two reviewers using the Appraisal of Guidelines Research and Evaluation (AGREE) II and Guideline Implementability Appraisal (GLIA) tools, respectively.Results12 documents containing guidance on CLTI referrals were included. Five were clinical practice guidelines. Nine targeted clinicians in the community among their audience, yet only one included a primary care clinician in their author group. Recommendations on identification and referral of CLTI were often in non-specific language and frequently assumed specialist knowledge of vascular disease. Just 4 of the 93 behaviour change techniques were identified in the guidance documents. Three relevant domains of the AGREE II tool were scored for five clinical practice guidelines: stakeholder involvement (range 21.4%–52.4%, mean 42.9%), clarity of presentation (range 71.4%–92.9%, mean 82.9%) and applicability (25.0%–57.1%, mean 36.8%). The GLIA tool identified barriers to ease of implementation for all five clinical practice guidelines.ConclusionsMost guidance for clinicians in the community on the management of CLTI has been written without their input and assumes knowledge of vascular disease, which may be lacking. Future guidance development should involve community clinicians, consider using additional behaviour change techniques, and improve the applicability and ease of implementation of recommendations.
Perinatal factors and early neonatal outcomes of abnormal birthweight infants in Hangzhou, China, 2015–2021: a retrospective cohort study
Authors: Chen Yiming , Zhang Huimin , Jiang Yan , Ning Wenwen , Huang Lingling , Wang Yanan , Chu Xuelian 
Published: May 2024

BackgroundThis study aimed to investigate the perinatal factors and early neonatal outcomes of abnormal birth weight (ABW) in Hangzhou, China from 2015 to 2021.MethodsA retrospective cohort study was designed to analyse the data of 76 847 newborns, in which the case groups included 3042 cases of low birth weight (LBW) and 2941 cases of fetal macrosomia (MAC), and 70 864 cases of normal weight were as the reference group.ResultsThe incidence of LBW and MAC was 3.96% and 3.83% in Hangzhou, China from 2015 to 2021. Prematurity (<37 weeks), multiple births, hospitalisation >7 days, fetal anomalies, caesarean section, pregnancy complications, maternal coinfection with pathogens and summer births would be correlated with the incidence of LBW (ORs=43.50, 7.60, 2.09, 1.89, 1.57, 1.28, 1.19 and 1.18, all p<0.05). Factors such as post-term pregnancy (>41 weeks), scarred uterus, anterior vaginal incision and gravidity ≥2 were correlated with decreased incidence of LBW, with ORs of 0.05, 0.54, 0.65 and 0.80. Moreover, caesarean delivery, post-term pregnancy (> 41 weeks), parity ≥1, lateral vaginal incision, gravidity ≥2, hospitalisation >7 days, winter births and pregnancy complications also have association with the incidence of MAC (ORs=3.92, 2.73, 2.19, 1.87, 1.22, 1.20, 1.17 and 1.13, all p<0.05) while prematurity (<37 weeks), scarred uterus and anterior vaginal incision have close association with decreased incidence of MAC, with ORs of 0.07, 0.21 and 0.74 (all p<0.05).ConclusionThere was a trend of yearly increase in ABW in Hangzhou, China from 2015 to 2021. Several neonatal and maternal-related variables such as caesarean section, pregnancy complications and hospitalisation >7 days are associated with the odds of LBW and MAC, however, factors such as pregnancy with scarred uterus relate to the decrease of ABW. Close monitoring and intervention during pregnancy are essential to reduce the occurrence of ABW.
Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis
Authors: Ramaswamy Viraraghavan V , Kumar Gunjana , Abdul kareem Pullattayil , Somasekhara Aradhya Abhishek , Suryawanshi Pradeep , Sahni Mohit , Khurana Supreet , Sharma Deepak , More Kiran 
Published: May 2024

BackgroundThere exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonatesObjectiveTo compare the efficacy of various interventions used to treat TCIMethodsMedline and Embase were searched from inception to 21stJuly 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.InterventionsDopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo.Main outcome measuresMortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author).Results15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment.ConclusionsEpinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.
INTEGRATION INTO GLOBAL VALUE CHAINS: EMPIRICAL EVIDENCE FROM RUSSIAN ENTERPRISES ON BARRIERS TO THE INNOVATION-EXPORT NEXUS
Authors: ROUD VITALIY , VLASOVA VALERIYA , THURNER THOMAS WOLFGANG 
Published: May 2024

Little is known about the different barriers that firms face as they advance with their technology uptake and tap into new markets. We show on a sample of 36,900 industrial enterprises that inwards-oriented firms had access to financial means but shied away from the economic risks associated with innovation activities. Exporters see opportunities for their innovation projects, but shy away from the investments needed. The failure to provide a supportive eco-system for innovation is one of the reasons why Russian manufacturers have not succeeded to integrate into global supply chains beyond the territories of the former Soviet Union.
Relationships between Body Composition Measurements and Insulin-Stimulated Plasma Lipoprotein Lipase Activity in Individuals with Varying Degrees of Body Adiposity
Authors: Johnsson Kailin , Freitas Eduardo , DeFilippis Eleanna , Roust Lori , Katsanos Christos 
Published: May 2024

Lipoprotein Lipase (LPL) hydrolyzes plasma triglycerides into free fatty acids in the circulation for use and/or storage in tissues (i.e., adipose tissue, skeletal muscle). Impaired LPL activity (LPLa) is associated with unfavorable health outcomes, such as elevated plasma triglyceride concentrations. We sought to determine how plasma LPLa relates to body composition measurements in individuals with varying degrees of adiposity. Eighteen subjects (ages 19 to 45 years) with body mass index (BMI) between 18 and 45 kg/m2 had their body composition measured by dual-energy X-ray absorptiometry (DEXA) and insulin sensitivity estimated from an oral glucose tolerance test by using the Matsuda Index (MI). Subjects ingested a bolus of 5g fat (i.e., whipping cream, 0.2 g fat/kg fat free mass), followed by small boluses of fat over the course of a 3-hour experimental period. This experimental protocol allows for the induction of a postprandial state without perturbation of the plasma triglyceride or insulin concentrations. LPLa was measured in the presence of increased plasma insulin induced by intravenous insulin infusion during the last 30 mins of the 3-hour experimental protocol. Insulin was infused at a rate of 0.5 mU/kg/min for subjects with MI-determined insulin sensitivity < 4 and 1 mU/kg/min for those with MI-determined insulin sensitivity > 4, in order to produce comparable levels of plasma insulin concentrations across subjects. To release endothelial-bound LPL, subjects received an injection of intravenous heparin (75 UI/kg) at the end of the plasma insulin infusion. Plasma samples were collected 10 minutes after the heparin infusion and analyzed for LPL concentration (LPLc) and LPLa using commercially available ELISA kits. Person’s correlation was used to evaluate relationships between several body composition parameters and LPLc as well as LPLa. LPLc was not correlated (P >0.05) with BMI (r = 0.03), total lean body mass (r = -0.20), total body fat (r = -0.02), or android fat (r = - 0.08). However, LPLa was positively correlated (P <0.05) with BMI (r = 0.49) and total lean body mass (r = 0.58), as well as total body fat (r = 0.54, P = 0.02) and android fat (r = 0.58, P = 0.01). In conclusion, increased body fat, including android fat, are associated with increased intravascular LPLa in the presence of insulin. Greater insulin-stimulated intravascular LPLa can enhance the release of triglyceride-associated free fatty acids and their uptake by tissues, resulting in insulin resistance as documented in individuals with increased android fat distribution. American Diabetes Association Grant #7-12-CT-40. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
ACE2 and a Traditional Chinese Medicine Formula NRICM101 Could Alleviate the Inflammation and Pathogenic Process of Acute Lung Injury
Authors: Lin Cheng-Han 
Published: May 2024

The coronavirus disease 2019 (COVID-19) is a highly transmittable respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and acute lung injury (ALI) is the major complication of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal model. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic application. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of human angiotensin-converting enzyme type II (ACE2) and the administration of the Chinese herbal prescription Chingguan Yihau (NRICM101) in ALI. The mice with ACE2 genetic modifications, including the overexpression of human ACE2 (K18-hACE2 TG) and the absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid to induce ALI. The acid intratracheal instillation induced the imbalance between angiotensin-converting enzyme (ACE) and ACE2 (i.e., ACE/ACE2), severe immune cell infiltration, cytokine storms, inflammatory effect, and pulmonary disease in the mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines Interleukin-6 (IL-6) and Tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid, histological evidence of lung injury, the production of the ACE expression, and the activation of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression. The results indicate that overproduction of ACE2 and induction of the ACE2-Ang-(1-7)/Mas axis could counteract the proinflammatory effect of acid-induced ALI and effectively alleviate the pathogenic process of acid-induced ALI by regulating MAPK, p-ERK1/2, and p-STAT3 pathways and dysregulation of MMP-2/MMP-9 activation. In addition, NRICM101, which is an effective TCM that has both antiviral and anti-inflammatory effects against COVID-19, shows potential for treating acid-induced ALI. NRICM101 could alleviate the disease progression of acid-induced ALI by suppressing IL-6 and TNF-α production in alveoli. In conclusion, the established mouse model provided an effective platform for researchers to investigate the role of ACE2 on pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related pulmonary diseases. The effects of NRICM101 administration is a potential strategy for curing acid-induced ALI evaluated in the mouse model in this study. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Multidimensional analysis of twin sets during an intensive week-long meditation retreat
Authors: Chitteti Ramamurthy , Hertz Juan P. Zuniga , Simpson Sierra , Hsu Chang Francis , Huang Han-Ping , Diamant Alex Jinich- , Chernov Andrei V. 
Published: May 2024

Meditation and other alternative practices have long been known to promote various health benefits, presumably by fostering a blood and tissue environment that enhances resilience to stress. Here, we used an integrated, multidisciplinary approach that couples quantitative electroencephalography (qEEG), biometrics, molecular, and biochemical data at multiple time points to investigate the impact of mind-based interventions on the body in a cohort of twins during an intensive week-long meditation retreat. We aim to show the feasibility of a novel design aimed to address individual changes controlling for intersubject trait variation (via twin control) and explore the role of genetic background on multi-omic factors during meditation. Interestingly, similar patterns of change in brain activity, network properties, and complexity were observed in the twin sets. These similarities were not observed in mismatched twin pairs. Heart rate dynamics studies showed alignment among twin pairs that was not present between unmatched pairs. In addition, changes in gene expression, metabolites, and cytokines present in blood plasma and associated with specific meditative states showed patterns of change associated by timepoint. Twin sets were similar in multiple domains before the start of the retreat, showed larger divergence at the mid-point, and looked more similar by the end of the retreat. To our knowledge, this study is novel within the twin research paradigm and is a first step towards exploring the effects of meditation in twins. InnerScience Research Fund. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Blood pressure-associated non-coding single nucleotide polymorphism rs217727 modulates gene expression in human endothelial cells
Authors: Pandey Rajan , Liu Yong , Liu Pengyuan , Therani Bhavika , Liang Mingyu 
Published: May 2024

Majority of Blood Pressure (BP)-associated single nucleotide polymorphisms (SNPs) are in intronic or intergenic regions. Allele G of the noncoding SNP rs217727 is associated with decreased systolic, diastolic and pulse pressure. MRPL23 is the closest protein-coding gene to rs217727, and the transcriptional start site of MRPL23 is 48.3kb away from rs217727. rs217727 is an expression quantitative trait locus for MRPL23 and TNNT3 (76.1kb away). We performed a series of studies to experimentally identify genes modulated by rs217727 and to begin to understand the mechanism. We differentiated a human induced pluripotent stem cell (iPSC) line to endothelial cells (iECs). The iECs were purified using VE-cadherin sorting. Chromatin conformation analysis using Micro-C identified several genes including MRPL23, IGF2 (141.6kb away) and TNNT3 as sharing a chromatin loop with rs217727. We used CRISPR-Cas9 to generate isogenic iPSC lines with either homozygous low BP (G) or high BP allele (A) of rs217727. The screening of several hundred clones led to the establishment of three and four clones with low BP and high BP genotypes. The edited iPSC lines were subjected to six rounds of differentiation to iECs for targeted real-time PCR analysis of genes near rs217727, including the genes mentioned above. We found significantly (p<0.05) decreased expression of TNNT3 (0.44±0.04 fold), LSP1 (142.6kb away; 0.12±0.02 fold) and IGF2 (0.78±0.06 fold) and slightly increased expression of CD81 (380.5kb away; 1.09±0.03 fold) in iECs with the high BP allele (n≥43) compared to the low BP allele (n≥34) of rs217727 (p<0.05). TNNT3 encodes troponin T3 fast skeletal type, LSP1 encodes lymphocyte specific protein 1 and IGF2 encodes insulin-like growth factor 2. The closest gene MRPL23, CTSD (231.8kb away), and MRPS6, a gene on a different chromosome, were not significantly differentially expressed. In summary, the results indicate that rs217727 influences the expression of several local genes in an allele-specific manner. The results provide new insights into the function of a BP-associated noncoding SNP. The work is supported by NHLBI P01 HL149620. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
High content omega-3 fish oil co-treatment maintains proper bone physiology in glucocorticoid treated autoimmune mice
Authors: Rahman Md , Ali Zayana , Tahsin Maisha , Kizhakayil Dhanya , Ibrahim Khadega , Cugno Chiara 
Published: May 2024

Despite the known side effects of glucocorticoid therapy, such as a higher risk of osteoporosis, fractures, and reduced bone density, it remains a frequently prescribed treatment for autoimmune disorders due to its strong anti-inflammatory and immunosuppressive properties. If strategies could be identified to reduce the side effects commonly associated with glucocorticoid use, it could lead to more frequent and safer use of this treatment option for autoimmune diseases. In this work, the combined effects of high content omega-3 fish oil (HCW3FO) and a synthetic glucocorticoid, methylprednisolone (MP) medication are investigated in relation to bone mineral density (BMD) reduction in arthritis prone female MRL-lpr/lpr mice. Two treatment groups were introduced to the mice when they were 4 months old: one group was given weekly injections of PBS, while the other group was given either 5 mg/kg MP or 20 mg/kg MP. Additionally, both groups were provided with the AIN93M diet, supplemented with either 4% corn oil or 4% HCW3FO daily, for a duration of 8 weeks. Prior to initiating the drug injections and dietary modifications, the mice underwent dual energy x-ray absorptiometry (DXA) scans to establish their baseline BMD values. To find out their ultimate BMD values, the mice underwent another DXA scan eight weeks later, right before being sacrificed. Over the course of eight weeks, the MP treatment did not lead to a significant reduction in BMD across various bone regions, except for the lumbar regions. Similarly, the HCW3FO treatment alone did not offer protection against BMD loss in MRL-lpr/lpr mice. However, when MP and HCW3FO were combined, it resulted in a remarkable preservation of BMD in different bone regions. This enhanced protection against BMD loss was associated with a reduced number of tartrate-resistant acid phosphatase (TRAP) positive areas and an increased number of alkaline phosphatase (ALP) positive areas in tibial sections as revealed by immunohistochemistry. Our findings provide compelling evidence that the combination of MP and HCW3FO maintains bone health in arthritis-prone MRL-lpr/lpr mice by promoting a balance between bone resorption and bone formation. Co-treatment with HCW3FO may hold promise as a potential strategy for preventing bone deterioration induced by long-term glucocorticoid therapy. Before moving on to clinical trials, more in vitro research into the mechanisms should be carried out alongside preclinical studies in mice with inflammatory diseases. QUCG-CAS-2122-2. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.