bluuebunny/crossref_metadata_2025_split huggingface dataset:
High sugar diet-induced insulin resistance in glia impairs axonal clearance after injury by downregulating Draper signaling
Authors: Alassaf Mroj , Rajan Akhila 
Published: May 2023

Obesity significantly increases the risk for developing neurodegenerative disorders, yet the precise mechanisms underlying this connection remain unclear. Defects in glial phagocytic function is a key feature of neurodegenerative disorders, as delayed clearance of neuronal debris can result in inflammation, cytotoxicity, secondary neuronal death, and poor nervous system recovery. Whether or how diet-induced obesity disrupts glial phagocytosis is unknown. Here, using a Drosophila diet-induced obesity model, we show that subjecting adult flies to a chronic high sugar diet (HSD) treatment delays the clearance of degenerating axons by causing glial insulin resistance. We find that HSD downregulates the basal and injury-induced expression of the glia-associated phagocytic receptor, Draper. Genetically inducing Insulin release from the Insulin producing cells (IPCs) phenocopies the HSD-induced Draper downregulation and insulin resistance, while attenuating insulin release from the IPCs rescues HSD-induced Draper downregulation and insulin resistance. Significantly, we show that genetically stimulating Phosphoinositide 3-kinase (PI3K), a downstream effector of Insulin receptor signaling rescues HSD-induced glial defects. Together, we provide mechanistic insights into how HSD alters glial phagocytic function in the adult brain. This is the full abstract presented at the American Physiology Summit 2023 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.
Targeted pharmacological inhibition of neuraminidase-3 ameliorates vascular dysfunction in diabetic mice
Authors: Foote Christopher , Ramirez-Perez Francisco , Jurrissen Thomas , Power Gavin , Morales-Quinones Mariana , Betancourt-Cortes Edgar , Lazo-Fernandez Yoskaly , Augenreich Marc , Manrique-Acevedo Camila , Padilla Jaume , Martinez-Lemus Luis 
Published: May 2023

In type 2 diabetes (T2D), endothelial dysfunction and arterial stiffening play a significant role in the development of cardiovascular disease. A central mediator of vascular dysfunction is degradation of the endothelial glycocalyx, a semipermeable mechanosensitive structure that separates the endothelium from the flow of blood and shear forces associated with it. Neuraminidase, a sialidase that cleaves sialic acid from the terminal branches of glycoproteins and glycolipids, is implicated in glycocalyx degradation. However, its role in mediating vascular dysfunction in the setting of T2D remains relatively unexplored. Herein we tested the hypothesis that increased neuraminidase-3 (Neu3) activity impairs vascular function, while its targeted inhibition improves it in diabetes. In support of this hypothesis, we report that mice overexpressing Neu3 exhibit increased blood pressure and pulse wave velocity, indicative of increased arterial stiffness. Furthermore, we show that pharmacological inhibition of Neu3 for 28 days in diabetic ( i.e., db/db) mice (vs. vehicle control) resulted in reduced pulse wave velocity, with no change in blood pressure. Neu3 inhibition also reduced stiffness in aortic explants, as assessed via atomic force microscopy. Excised arteries were also assessed for flow-mediated dilation and vascular stiffness using pressure myography. Arteries from diabetic mice treated with the Neu3 inhibitor had increased flow-mediated dilation and reduced incremental modulus of elasticity, indicative of improved endothelial function and reduced arterial stiffness. Collectively, these data support the hypothesis that Neu3 is a potential therapeutic target for the amelioration of vascular dysfunction in T2D. National Institutes of Health grant: R01HL153264 to LM-L and JP This is the full abstract presented at the American Physiology Summit 2023 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.
Framework for precision phenotyping of heart failure patients using clinical data at rest and exercise
Authors: Carlson Brian , Meyer Andrew , Ježek Filip , Jones Edith , Hua Xinwei , Hummel Scott , Tang Yida , Beard Daniel 
Published: May 2023

Precision phenotyping of mechanistic differences between and within different types of heart failure is a valuable tool not only to understand the range of underlying cardiovascular dysfunction but to identify patients who could benefit from a targeted treatment or procedure. Our group previously has used standard clinical hemodynamic measures at rest coupled with a computational model of the cardiovascular system to identify differences between patients diagnosed with heart failure with preserved ejection fraction (HFpEF). Even though this effort has proven fruitful, many patients with HFpEF exhibit symptoms only during exercise. We hypothesize that incorporating exercise metrics into our approach will improve discrimination between HFpEF phenotypes. In this study we have expanded the pool of clinical data to include cardiopulmonary exercise testing (CPET) data and added to the complexity of our cardiovascular system model to simulate exercise. Data were collected prospectively from both Peking University Third Hospital and the University of Michigan and include measures from right heart catheterization (RHC) at rest and at exercise along with transthoracic echocardiography (TTE) at rest. The measures for each patient are used to identify our expanded cardiovascular systems model which now can inform parameters related to the strength of sarcomeric contraction in the left, septal and right ventricular walls, left and right atrial elastance in addition to predicting left ventricular and right ventricular cardiac power at rest and exercise. Based on the preliminary data acquired, we present a framework that can quantify underlying differences between HFpEF patients using unsupervised machine learning to find distinct HFpEF phenogroups, using clinical data both at rest and during exercise. Michigan Medicine/Peking University Health Science Center Joint Institute for Translational and Clinical Research This is the full abstract presented at the American Physiology Summit 2023 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.
Detecting unique analyte-specific radio frequency spectral responses in liquid solutions -- implications for non-invasive physiologic monitoring
Authors: Klyve Dominic , Bosua Phil , Somers Virend , Anderson James 
Published: May 2023

With rising healthcare costs and the rapid increase in remote physiologic monitoring and care delivery, there is increasing need for economical, accurate and non-invasive continuous measures of blood analytes. Based on radio-frequency identification (RFID), we have developed a novel electromagnetic platform technology (the Bio-RFID platform) to non-invasively penetrate inanimate surfaces, capture data from individual radio frequencies, and convert those data into physiologically meaningful information and insights. Here we describe ground-breaking proof-of-principle studies using Bio-RFID to accurately measure various concentrations of analytes in deionized water. The in vitro Bio-RFID platform consists of an acrylic cuvette in the shape of a 4 inch x 4 inch x 8 inch rectangular prism mounted on the Bio-RFID sensor. This apparatus is in turn mounted on a balance that allows the determination of the mass of the analyte being scanned to within 0.1g. The hardware scans through several thousand radio frequencies and sends the data to proprietary software running on a laptop computer. The software displays a spectral scan known as the Bio-RFID signature of the analyte and computes a similarity metric to compare different signatures.We tested the hypothesis that the Bio-RFID platform is able to precisely and non-invasively measure and identify a variety of analytes in vitro. For this assessment, varying solutions of 1) water in isopropyl alcohol; 2) salt in water; and 3) commercial bleach in water were tested, using a randomized double-blind trial design, as proxies for biochemical solutions in general. The Bio-RFID technology was able to detect concentrations of 2000 parts per million (ppm), with evidence suggesting the ability to detect considerably smaller concentration differences. The novel application of a Bio-RFID electromagnetic platform technology accurately detects, measures, and quantifies specific molecules in liquid. While these findings have in vitro commercial applications, these proof-of-principle studies provide strong support for the application of Bio-RFID technology for non-invasive bio-monitoring of physiologically and medically relevant analytes, such as alcohol and glucose, in the human body. These studies were funded by a grant from Know Labs to Mayo Clinic. PB and JHA are employed by Know Labs. VKS and Mayo Clinic acknowledge a financial interest in Know Labs. This is the full abstract presented at the American Physiology Summit 2023 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.
Use of compensatory reserve measurements to reassess the sensitivity and specificity of the shock index for early and accurate detection of reduced central blood volume status
Authors: Convertino Victor , Thompson Patrick , Koons Natalie , Le Tuan , Lanier Jeffrey , Cardin Sylvain 
Published: May 2023

Background: Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared to either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: 1) presents a late signal of central blood volume status; 2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and 3) cannot identify individuals at greatest risk for the onset of circulatory shock. Methods: We measured HR, SBP and CRM in 172 human subjects (19 to 55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high (HT; n = 118) and low (LT; n = 54) tolerance based on completion of 60 mmHg LBNP. The time course relationship between SI and CRM was determined and Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI. Results: The time and level of LBNP required to reach a SI = 0.9 (~60 mmHg LBNP) was significantly greater (P < 0.001) compared to CRM that reached 40% at ~40 mmHg LBNP. SI did not differ between HT and LT subjects at 45 mmHg LBNP levels. ROCAUC for CRM was 0.95 (95%CI = 0.94-0.97) compared to 0.91 (0.89-0.94) for SI (P = 0.0002). Conclusions: Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia. This is the full abstract presented at the American Physiology Summit 2023 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.
Quantitative multiplex real-time polymerase chain reaction assay for the detection of Helicobacter pylori and clarithromycin resistance
Authors: Kim Ilsoo , Maeng Lee-So , Kim Joon Sung , Kim Byung-Wook , Cheung Dae Young , Kim Jin Il , Park Soo-heon 
Published: May 2023

Abstract
Background
Identifying clarithromycin resistance is essential for eradicating Helicobacter pylori (HP). Therefore, we evaluated the performance of Allplex™ H.pylori & ClariR Assay (Allplex™) for diagnosing and detecting clarithromycin resistance in HP.

Methods
Subjects who underwent esophagogastroduodenoscopy between April 2020 and August 2021 at Incheon St. Mary’s hospital were enrolled in this study. The diagnostic performances of Allplex™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with sequencing as the gold standard.

Results
A total of 142 gastric biopsy samples were analyzed. Gene sequencing revealed 124 HP infections, 42 A2143G mutations, 2 A2142G mutations, one dual mutation, and no A2142C mutation. DPO-PCR showed 96.0% sensitivity and 100.0% specificity for HP detection; the corresponding rates for Allplex™ were 99.2% and 100.0%. DPO-PCR showed 88.3% sensitivity and 82.0% specificity for A2143G mutation, and Allplex™ showed 97.6% and 96.0%. The Cohen’s Kappa coefficient for overall test results was 0.56 for DPO-PCR and 0.95 for Allplex™.

Conclusion
Allplex™ showed comparable diagnostic performance with direct gene sequencing and non-inferior diagnostic performance to DPO-PCR. Further research is required to confirm whether Allplex™ is an effective diagnostic tool for the eradication of HP.
Ketamine versus etomidate for rapid sequence intubation in patients with trauma: a retrospective study in a level 1 trauma center in Korea
Authors: Kim Jinjoo , Jung Kyoungwon , Moon Jonghwan , Kwon Junsik , Kang Byung Hee , Yoo Jayoung , Song Seoyoung , Bang Eunsook , Kim Sora , Huh Yo 
Published: May 2023

Abstract
Background
Ketamine and etomidate are commonly used as sedatives in rapid sequence intubation (RSI). However, there is no consensus on which agent should be favored when treating patients with trauma. This study aimed to compare the effects of ketamine and etomidate on first-pass success and outcomes of patients with trauma after RSI-facilitated emergency intubation.

Methods
We retrospectively reviewed 944 patients who underwent endotracheal intubation in a trauma bay at a Korean level 1 trauma center between January 2019 and December 2021. Outcomes were compared between the ketamine and etomidate groups after propensity score matching to balance the overall distribution between the two groups.

Results
In total, 620 patients were included in the analysis, of which 118 (19.9%) were administered ketamine and the remaining 502 (80.1%) were treated with etomidate. Patients in the ketamine group showed a significantly faster initial heart rate (105.0 ± 25.7 vs. 97.7 ± 23.6, p = 0.003), were more hypotensive (114.2 ± 32.8 mmHg vs. 139.3 ± 34.4 mmHg, p < 0.001), and had higher Glasgow Coma Scale (9.1 ± 4.0 vs. 8.2 ± 4.0, p = 0.031) and Injury Severity Score (32.5 ± 16.3 vs. 27.0 ± 13.3, p < 0.001) than those in the etomidate group. There were no significant differences in the first-pass success rate (90.7% vs. 90.1%, p > 0.999), final mortality (16.1% vs. 20.6, p = 0.348), length of stay in the intensive care unit (days) (8 [4, 15] (Interquartile range)), vs. 10 [4, 21], p = 0.998), ventilator days (4 [2, 10] vs. 5 [2, 13], p = 0.735), and hospital stay (days) (24.5 [10.25, 38.5] vs. 22 [8, 40], p = 0.322) in the 1:3 propensity score matching analysis.

Conclusion
In this retrospective study of trauma resuscitation, those receiving intubation with ketamine had greater hemodynamic instability than those receiving etomidate. However, there was no significant difference in clinical outcomes between patients sedated with ketamine and those treated with etomidate.
Extrapolating empirical long-term survival data: the impact of updated follow-up data and parametric extrapolation methods on survival estimates in multiple myeloma
Authors: Bakker LJ , Thielen FW , Redekop WK , Groot CA Uyl-de , Blommestein HM 
Published: May 2023

Abstract
Background
In economic evaluations, survival is often extrapolated to smooth out the Kaplan-Meier estimate and because the available data (e.g., from randomized controlled trials) are often right censored. Validation of the accuracy of extrapolated results can depend on the length of follow-up and the assumptions made about the survival hazard. Here, we analyze the accuracy of different extrapolation techniques while varying the data cut-off to estimate long-term survival in newly diagnosed multiple myeloma (MM) patients.

Methods
Empirical data were available from a randomized controlled trial and a registry for MM patients treated with melphalan + prednisone, thalidomide, and bortezomib- based regimens. Standard parametric and spline models were fitted while artificially reducing follow-up by introducing database locks. The maximum follow-up for these locks varied from 3 to 13 years. Extrapolated (conditional) restricted mean survival time (RMST) was compared to the Kaplan-Meier RMST and models were selected according to statistical tests, and visual fit.

Results
For all treatments, the RMST error decreased when follow-up and the absolute number of events increased, and censoring decreased. The decline in RMST error was highest when maximum follow-up exceeded six years. However, even when censoring is low there can still be considerable deviations in the extrapolated RMST conditional on survival until extrapolation when compared to the KM-estimate.

Conclusions
We demonstrate that both standard parametric and spline models could be worthy candidates when extrapolating survival for the populations examined. Nevertheless, researchers and decision makers should be wary of uncertainty in results even when censoring has decreased, and the number of events has increased.
Implementation of continuous-wave Doppler ultrasound to detect the high-risk foetus in the low-risk mother: lessons from South Africa
Authors: Hlongwane Tsakane M.A.G. , Pattinson Robert C. , Bergh Anne-Marie 
Published: May 2023

Abstract
Introduction
Detecting the risk of stillbirth during pregnancy remains a challenge. Continuous-wave Doppler ultrasound (CWDU) can be used to screen for placental insufficiency, which is a major cause of stillbirths in low-risk pregnant women. This paper describes the adaptation and implementation of screening with CWDU and shares critical lessons for further rollout. Screening of 7088 low-risk pregnant women with Umbiflow™ (a CWDU device) was conducted in 19 antenatal care clinics at nine study sites in South Africa. Each site comprised a catchment area with a regional referral hospital and primary healthcare antenatal clinics. Women with suspected placental insufficiency as detected by CWDU were referred for follow-up at the hospital. A 35–43% reduction in stillbirths was recorded.

Methods
The authors followed an iterative reflection process using the field and meeting notes to arrive at an interpretation of the important lessons for future implementation of new devices in resource-constrained settings.

Results
Key features of the implementation of CWDU screening in pregnancy combined with high-risk follow-up are described according to a six-stage change framework: create awareness; commit to implement; prepare to implement; implement; integrate into routine practice; and sustain practice. Differences and similarities in implementation between the different study sites are explored. Important lessons include stakeholder involvement and communication and identifying what would be needed to integrate screening with CWDU into routine antenatal care. A flexible implementation model with four components is proposed for the further rollout of CWDU screening.

Conclusions
This study demonstrated that the integration of CWDU screening into routine antenatal care, combined with standard treatment protocols at a higher-level referral hospital, can be achieved with the necessary resources and available maternal and neonatal facilities. Lessons from this study could contribute to future scale-up efforts and help to inform decisions on improving antenatal care and pregnancy outcomes in low- and middle-income countries.
Experiences of childbirth care among immigrant and non-immigrant women: a cross-sectional questionnaire study from a hospital in Norway
Authors: Reppen Kristin , Henriksen Lena , Schei Berit , Magnussen Elisabeth Balstad , Infanti Jennifer Jean 
Published: May 2023

Abstract
Background
Immigrant women have higher risks for poor pregnancy outcomes and unsatisfactory birth experiences than the general population. The mechanisms behind these associations remain largely unknown, but they may result from differential care provided to immigrant women or unsatisfactory interactions with health providers. This study aimed to investigate immigrant and non-immigrant women's experiences of health care during childbirth, particularly assessing two dimensions: perceived general quality of care and attainment of health care needs during childbirth.

Methods
This was a cross-sectional study carried out over 15 months in 2020 and 2021, and data were collected from a self-completed questionnaire. The labour and birth subscale from the Experience of Maternity Care questionnaire was used to assess the primary outcome of care experiences. A total of 680 women completed the questionnaire approximately within two days after birth (mean 2.1 days) at a hospital in Trondheim, in central Norway. The questionnaire was provided in eight languages.

Results
The 680 respondents were classified as immigrants (n = 153) and non-immigrants (n = 527). Most women rated their quality of care during childbirth as high (91.5%). However, one-quarter of the women (26.6%) reported unmet health care needs during childbirth. Multiparous immigrant women were more likely than multiparous non-immigrant women to report that their health care needs were unmet during childbirth (OR: 3.31, 95% CI: 1.91–5.72, p < 0.001, aOR: 2.83, 95% CI: 1.53–5.18, p = 0.001). No other significant differences between immigrant versus non-immigrant women were found in subjective ratings of childbirth care experiences. Having a Norwegian-born partner and a high level of Norwegian language skills did not influence the immigrant women's experience of childbirth care.

Conclusions
Our findings indicate that many women feel they receive high-quality health care during childbirth, but a considerable number still report not having their health care needs met. Also, multiparous immigrant women report significantly more unmet health care needs than non-immigrants. Further research is required to assess immigrant women's childbirth experiences and for health care providers to give optimal care, which may need to be tailored to a woman's cultural background and individual expectations.